The development of the adrenal gland zona glomerulosa in the rat. A morphological, immunohistochemical and biochemical study

We have studied the development of the adrenal gland in the rat comprising the ages ranging from 0 to 90 days after birth. The weight of the animals and that of the adrenal glands demonstrated a linear growth with time until 75 days, both in males and females. The area of the zona glomerulosa (ZG) increased in size from birth until ≈40 days of age. After that, growth had a much smaller slope (females, r=0.84, P<0.001; males, r=0.81, P<0.001). Aldosterone secretion had a marked increase until 20 days of age and thereafter demonstrated a tendency for a decrease (females, r=−0.19, P<0.02; males r=−0.26, P<0.001). Plasma renin activity followed a trend parallel to that of aldosterone. The steroid precursor 18-OH-deoxycorticosterone (18-OH-DOC) demonstrated a different course as it increased progressively with age especially in the females (females, r=0.57, P<0.001; males, r=0.40, P<0.001). The expression of the enzyme 3-β-hydroxysteroid dehydrogenase (3-β-HSD) was also studied by immunohistochemistry and it was shown to be very low at birth and starting to increase by 10 days of age. After 30/40 days of age the amount of this enzyme existing in the ZG was comparable with that of the outer zona fasciculata (ZF). We conclude that the development of the ZG in the rat has particularities that make it different from that of the rest of the cortex.     

Circulating erythropoietin in microalbuminuric type 2 diabetic patients with normal renal function: a pilot study

To verify the hypothesis of an early impairment of erythropoietin (Epo) production and to assess the adequacy of its circulating levels in diabetic nephropathy, we investigated Epo values in 18 microalbuminuric type 2 diabetic patients with normal renal function (7 anaemic and 11 nonanaemic), 24 subjects with uncomplicated iron-deficiency anaemia, and 15 healthy controls comparable for sex and age. Mean±S.D. plasma Epo level was 56.4±12.7 mU/mL in iron-deficient patients and 9.3±2.6 mU/mL in controls. In diabetic groups, mean±S.D. Epo level was 11.38±3.65 mU/mL in nonanaemic and 49.12±6.44 mU/mL in anaemic subjects. No significant difference (P>.05) in Epo values was found between controls and nonanaemic diabetic patients. Anaemic diabetics and iron-deficient subjects had significantly higher values than the nonanaemic groups (P>.001). An inverse significant relation between Epo levels and Hb concentration resulted in both anaemic diabetics (r=−.44, P>.05) and iron-deficient patients (r=−.61, P=.001). Analysis of covariance (P>.05) and comparison of the two regression lines (t=0.4, df=29, P>.05) did not show any significant difference between diabetic patients with anaemia and iron-deficient patients. These results suggest that normochromic anaemia observed in microalbuminuric diabetic patients with normal renal function is not due to Epo deficiency, and circulating levels of this hormone are suitably increased with regard to Hb concentration.     

Association between hematological parameters and metabolic syndrome components in a Chinese population

Insulin resistance, an essential core contributing to the metabolic syndrome (MS), has been demonstrated in some studies to be associated with white blood cell (WBC) or red blood cell (RBC) counts. The present study was undertaken to assess systemically the relationship between WBC or RBC counts and various clinical features of MS in a large Chinese population at Taiwan. A total of 4938 subjects (2891 men and 2047 women with a mean age of 50.1±12.6 years), who had attended health examination at this hospital were enrolled. The Adult Treatment Panel III (ATP III) definition of MS components was adopted in this study with the exception of the definition of obesity. This was defined as body mass index (BMI) greater than 27 kg/m². Overall, 14% had high serum total triglyceride (TG), 8% had low high-density lipoprotein (HDL) cholesterol, and 18% were obese. WBC counts showed a statistically significant (P<.001) correlation with TG (r=.265), HDL(r=−.187), fasting glucose (r=.084), and BMI (r=.172) but not with blood pressure levels. In addition, RBC counts correlated significantly (P<.001) with TG (r=.250), HDL(r=−.269), fasting glucose (r=.098), and BMI (r=.228). WBC and RBC counts in subjects grouped according to the presence of 0, 1, 2, and ≥ 3 features of MS were 6268±1633, 6555±1782, 6995±1880, and 7185±1696 cells/mm³, and 4.63±0.56×10⁶, 4.73±0.54×10⁶, 4.84±0.60×10⁶, and 4.91±0.55×10⁶ cells/mm³, respectively (P for trend <.001). Subjects in the highest quartile of WBC or RBC counts demonstrated a three- or twofold increase, respectively, in the odds ratio for MS with 3 or more metabolic features compared to subjects in the lowest quartile of WBC or RBC counts. Increased WBC and RBC counts, albeit normal, were associated with a variety of MS features in a Taiwan Chinese population, suggesting that hematological parameters could potentially be used as indicators of this syndrome.     

Segmental blood flow and rheological determinants in diabetic patients with peripheral occlusive arterial disease

Vascular abnormalities are more prevalent in the lower extremities in diabetic patients and may cause diminished perfusion to surrounding tissues. We sought to identify blood flow abnormalities in the leg of diabetic patients with peripheral occlusive arterial disease (POAD) and to determine whether these were associated with abnormalities in rheological determinants, namely, plasma fibrinogen concentration (PFC), relative plasma viscosity (RPV), hematocrit (Hct), and whole blood viscosity (WBV). Seventeen diabetic patients with POAD were compared with 40 diabetic patients without POAD and 19 nondiabetic control subjects. Blood flow was measured by venous occlusion plethysmography, RPV was measured by capillary viscometry, WBV was measured by a Wells–Brooksfield viscometer [at high (230 s⁻¹) and low (23 s⁻¹) shear rates], and PFC was measured by the clot–weight method of Ingram [Ingram, G. I. C. (1961). A suggested schedule for the rapid investigation of acute haemostatic failure. Journal of Clinical Pathology, 14, 356–360]. Ankle blood flow (Q_ak) was significantly lower in diabetic patients with POAD than in diabetic patients without POAD (P<.05). PFC was higher and Hct was lower in diabetic patients with POAD than in diabetic patients without POAD (P<.05). RPV was 1.97±0.15 versus 1.92±0.15 in diabetic patients with POAD and diabetic patients without POAD, respectively (P>.05). There was no significant difference in WBV at low or high shear rates between the groups studied. There was a correlation between WBV at low shear rate and arterial flow in the calf (Q_c) (r=.94) and great toe (r=.95) in diabetic patients with POAD, and between Q_c and WBV at high (r=−.465) and low (r=−.472) shear rates in diabetic patients without POAD (P<.05). We conclude that vasodilatation occurring in diabetic patients without POAD is severely restricted or absent in diabetic patients with POAD. Increased plasma fibrinogen and plasma viscosity may contribute to this phenomenon.     

Influence of endogenous hyperinsulinism on high density lipoprotein2 level in type 2 (non-insulin-dependent) diabetes mellitus and impaired glucose tolerance

We determined the insulin response to an oral glucose ingestion and levels of serum lipoproteins in 25 untreated patients with type 2 diabetes mellitus, in 26 subjects with impaired glucose tolerance (IGT), and in 35 non-diabetic control subjects. The three groups had similar compositions with respect to age and sex distribution. The levels of VLDL triglycende in the subjects with type 2 diabetes or IGT were higher than those in controls. Serum HDL- and HDL₂ cholesterol were significantly decreased in type 2 diabetics, and the subjects with IGT showed a similar tendency. Serum apolipoprotein A-II levels were lower in the male subjects with type 2 diabetes or IGT than in controls. Insulin reponse, i.e., sum of immunoreactive insulin (IRI) levels at basal, 30, 60, 90 and 120 min after a 75-g oral glucose load, negatively correlated to HDL and HDL₂ cholesterol levels (r = −0.396, P < 0.05; r = −0.482, P < 0.001, respectively), and positively correlated to VLDL triglyceride values (r = 0.485, P < 0.001) in the male subjects with type 2 diabetes or IGT. In the female subjects, fasting plasma IRI values significantly correlated to HDL cholesterol (r = −0.496, P < 0.05). There was a significant negative correlation between the concentrations of HDL₂ cholesterol and VLDL trgglyceride. These data show that lipoprotein metabolism, not only in type 2 diabetics, but also in IGT tends to show changes such as decreased HDL₂ cholesterol and increased VLDL triglyceride levels, and which might be related to the hypersecretion of endogenous insulin.     

Erythrocyte sorbitol level as a predictor of the efficacy of epalrestat treatment for diabetic peripheral polyneuropathy

The relationship between the effect of aldose reductase inhibitors (ARIs) on the activation of the polyol pathway and on diabetic neuropathy has not been fully established. To address this issue, we investigated the effect of epalrestat (150 mg/day), an ARI, on erythrocyte sorbitol levels as an index of polyol activation and on nerve function test results in 43 patients with diabetic peripheral polyneuropathy. After 6 months of epalrestat administration, erythrocyte sorbitol levels did not decrease in patients as a whole. However, a decrease in erythrocyte sorbitol levels during epalrestat administration was significantly correlated with baseline erythrocyte sorbitol levels (ρ=−.47, P<.01): The higher the level at baseline, the greater the decrease after epalrestat treatment. Moreover, the mean sorbitol level during epalrestat treatment was associated with the beneficial effect of epalrestat on vibration sensitivity as measured with a C-128 tuning fork (ρ=−.66, P<.01) and/or a pallesthesiometer TM-31A (ρ=.53, P<.05). On the other hand, erythrocyte sorbitol levels did not reflect the prognosis of nerve conduction velocity. These findings at least partly suggest a causal relationship between polyol activation and the development of diabetic neuropathy. Aldose reductase inhibitor treatment may be clinically useful in the control of polyol activation, especially in patients with excessive accumulation of sorbitol.     

Study of the rate of early glucose disappearance following insulin injection: insulin sensitivity index

The euglycaemic hyperinsulinaemic glucose clamp is usually considered as the reference technique to evaluate insulin sensitivity. As it is an-expensive and time-consuming tool, we therefore tried to validate a simple insulin tolerance test (ITT) (IV bolus of 0.1 IU/kg of regular insulin, with glucose sampling at −5, 0, 3, 5, 7, 10 and 15 min) and to demonstrate its usefulness. Insulin sensitivity was measured by DG/G0 ratio (G0 = initial glycaemia, DG is the variation between G0 and the glycaemia obtained at 15 min by the calculation of the regression plot). We confirmed the existence of a correlation between the glucose uptake (mg/kg per min) evaluated by glucose clamp and the DG/G0 index (r = 0.9, P < 0.01). There was no stimulation of hormonal counter regulation during the test. The ITT was significantly correlated both with fasting insulin (r = −0.43, P < 0.01), and post-glucose load insulin concentration (r = −0.67, P < 0.01); each measurement expressing insulin sensitivity. Four groups of patients with different insulin sensitivity; controls, NIDDM, gynoid and android obese subjects, were clearly separated by ITT. We showed that fasting glycaemia and DG/G0 were correlated (y = 2.63/x − 0.093; r = 0.82, P < 0.01). These results suggest that ITT could be an easy, quick and low cost method to evaluate insulin resistance in clinical practice and epidemiological studies.     

Homocysteine and endogenous markers of renal function in type 2 diabetic patients without coronary heart disease

The aim of this study was to assess parameters of renal function and other determinants of plasma homocysteine in type 2 diabetic patients without coronary heart disease (CHD). Fasting plasma homocysteine, serum cystatin C and serum creatinine were determined in 183 (75 men, 108 women) Type 2 diabetic patients without clinical evidence of CHD. Creatinine clearance was calculated and parameters such as blood pressure, body mass index (BMI), and glycated haemoglobin (HbA_1c) were assessed. The urine albumin:creatinine ratio was used to classify patients as normo-, micro- or macroalbuminuric. One hundred and ten patients were normoalbuminuric, 67 patients were microalbuminuric and six patients were macroalbuminuric. There was no statistically significant difference in plasma homocysteine concentration between patients with normoalbuminuria and microalbuminuria. There was a trend towards increasing plasma homocysteine with decreasing glomerular filtration rate (GFR) (r=−0.46; P<0.0001). There was statistically significant correlation between plasma homocysteine and age (r=0.37), serum cystatin C (r=0.47), and serum creatinine (r=0.56). Plasma homocysteine concentration was significantly higher in patients with BMI<30 kg/m² and showed significant inverse correlation with weight (r=−0.16; P=0.03) and body mass index (r=−0.24; P=0.001). Homocysteine and serum creatinine were significantly higher in males than females and higher in smokers than non smokers but was not associated with glycemic control and duration of diabetes. In conclusion, elevated homocysteine concentration in patients with type 2 DM without CHD is related to age, gender, smoking, BMI and GFR. Follow up studies will provide further information on the association between hyperhomocysteinemia and the development of cardiovascular disease.     

Serum lipoprotein lipid concentration and composition in homozygous and heterozygous patients with cholesteryl ester transfer protein deficiency

Six homozygous, 10 heterozygous and 8 unaffected subjects in a CETP deficient family confirmed by CETP gene analysis were studied to characterize serum lipoproteins separated by ultracentrifugation, and to examine the relations between CETP levels and lipoprotein lipid concentration and composition. The serum CETP levels were measured by radioimmunoassay using ¹²⁵I-labeled monoclonal antibodies (TP2). The serum CETP levels in the homozygotes were undetectable and those in the heterozygotes were significantly lower than those in the unaffected subjects (1.5 ± 0.1 vs. 2.2 ± 0.5 μg/ml, P < 0.01). In the HDL fraction, esterified cholesterol (EC) levels in the homozygotes were significantly increased (P < 0.01), and those in the heterozygotes were slightly increased (n.s.), in comparison with those in the unaffected and the normolipidemic controls. The EC levels in the IDL fractions were lower in the homozygotes than in the normolipidemic controls. The EC/triglyceride (TG) molar ratios in IDL, the fraction obtained from the homo- and heterozygotes, were lower than those from the unaffected subjects (P < 0.01 and < 0.01, respectively), and the EC/TG ratios in the HDL fraction obtained from the homo- and heterozygotes were higher than those from the unaffected subjects (P < 0.01 and n.s., respectively). Linear regression analysis showed that positive correlates of the serum CETP levels in all subjects were: IDL-EC (r = 0.463), HDL-TG (r = 0.603) and VLDL- and IDL-EC/TG ratio (r = 0.698 and and 0.843). When the homozygotes were excluded from the analysis, the EC/TG ratios in VLDL IDL were still positively correlated with the serum CETP levels (r = 0.677 and 0.676). Inverse correlates of the serum CETP levels in all subjects were: HDL-EC (r = −0.783) and HDL-EC/TG ratio (r = −0.739). These results suggested that the decreased CETP concentration decreased IDL-cholesterol and increased HDL-cholesterol levels through reducing transport of EC from HDL to IDL, and produced an anti-atherogenic plasma lipoprotein pattern.     

Plasma ANP and cyclic GMP after physical exercise in patients with mitral valve disease and in healthy subjects

Plasma levels of both atrial natriuretic peptide (ANP) and cyclic GMP are elevated in patients with various heart diseases as compared to healthy subjects. In this study patients with advanced mitral valve disease (Group A) and healthy subjects (Group B) were exposed to symptom-limited upright stepwise physical exercise on a cycle ergometer. Concentrations of ANP and cyclic GMP were measured in plasma at rest (20 min in supine position) or 5 min after physical exercise by specific radioimmunoassays. Here we show that short dynamic exercise caused a significant increase in plasma levels of ANP and cyclic GMP, in both groups. In Group A strong correlation between plasma ANP and cyclic GMP was found at rest (r = 0.91, P < 0.001, n = 11) and after physical exercise (r = 0.85, P < 0.001, n = 11). In contrast, there was no correlation between plasma concentrations of ANP and cyclic GMP in Group B at rest (r = −0.16, P > 0.05, n = 10) or after exercise loading (r = 0.14, P > 0.05, n = 10). Absolute increases in circulating levels of both substances were not found to correlate in either group. These data suggest that exercise-induced elevations in plasma cyclic GMP may be due not only to ANP release but also to an as yet undetermined factor, possibly EDRF/NO.     

Dynamic change in collateral flow associated with myocardial ischemia in humans

Background: This study sought to investigate how collateral flow changes during myocardial ischemia in patients. Methods: Myocardial contrast echocardiography (MCE) and rapid atrial pacing were performed in 20 patients with angiographically evidenced coronary collaterals from the right coronary artery (RCA) to the occluded left anterior descending coronary artery. Sonicated contrast medium was injected into the RCA before and immediately after atrial pacing to determine the peak background-subtracted contrast intensity (PI) in the collateral territory (PIA) and its ratio to PI in the control territory (PI ratio) as parameters of collateral blood flow. Lactate production in the coronary circulation during pacing was determined to assess myocardial ischemia in the collateral territory. Results: PIA showed a significant correlation with regional wall motion either before (r(squared)=−0.64, P<0.01) or after pacing (r(squared)=−0.65, P<0.01). Similarly, PI ratio was significantly correlated with regional wall motion either before (r(squared)=−0.54, P<0.05) or after pacing (r(squared)=−0.64, P<0.01). Rapid atrial pacing decreased both PIA and PI ratio significantly greater in patients with lactate production than in those without (PIA: −67±53 vs. −15±34%, P<0.05; PI ratio: −68±49 vs. −8.2±32%, P<0.05, respectively), while neither PIA nor PI ratio differ between the two groups of patients before pacing (PIA: 13.8±19. vs. 16.2±13.3U, P=0.75; PI ratio: 0.70±0.71 vs. 0.87±0.65, P=0.58, respectively). Conclusions: We concluded that (1) collateral flow determined by MCE was closely associated with regional cardiac function, and (2) not the amount of collateral flow at rest, but pacing-induced change of collateral flow seemed to be a determinant of regional ischemia in patients with coronary collaterals.     

Proinsulin-like molecules and plasminogen activator inhibitor type 1 (PAI-1) activity in diabetic and non-diabetic subjects with and without myocardial infarction

Elevated plasminogen activator inhibitor type 1 (PAI-1) activity has been shown to correlate with plasma insulin, proinsulin-like molecules, serum triglycerides and insulin sensitivity in both non-insulin dependent diabetic (NIDDM) subjects and subjects with coronary heart disease. We examined the relative roles of these variables in determining PAI-1 activity in four groups of male caucasian subjects: non-diabetic subjects with (n=38) and without (n=38) previous myocardial infarction (MI) and NIDDM subjects with (n=26) and without (n=30) previous MI. Insulin and proinsulin-like molecules were measured using specific two-site immunometric assays and insulin sensitivity estimated using the Homeostasis Model Assessment (HOMA) model. Subjects were comparable in age and body mass index. In univariate analysis, there were significant correlations of PAI-1 activity with intact and des-31,32-proinsulin and serum triglycerides in non-diabetic subjects with (r=0.52, P=0.001; r=0.58, P<0.001; r=0.41, P=0.010) and without (r=0.31, P=0.056; r=0.46, P=0.006; r=0.41, P=0.011) MI, but not with plasma insulin or insulin sensitivity. In NIDDM subjects, PAI-1 activity correlated significantly with intact and des-31,32-proinsulin and serum triglyceride (r=0.47, P=0.015; r=0.58, P=0.002; r=0.44, P=0.026) only in subjects with MI. In multiple regression analysis, MI was the most important determinant of PAI-1 activity levels (r²=0.31, F=55.6, P<0.001). In conclusion, concentrations of proinsulin-like molecules and serum triglycerides appear to be stronger determinants of PAI-1 activity than plasma insulin or insulin sensitivity in both NIDDM subjects and non-diabetic subjects with and without MI. However, the relationship of MI with PAI-1 activity is independent of these variables.     

Inhibitory effect of prostaglandin E1 on intimal thickening following photochemically induced endothelial injury in the rat femoral artery

The inhibitory effect of prostaglandin E₁, which has an anti-platelet action and a vasodilating action via intracellular cyclic AMP elevation, was studied on intimal thickening in the rat femoral artery. A segment of the femoral artery was occluded by a platelet and fibrin-rich thrombus due to photochemical reaction between systemically administered Rose Bengal and transluminal green light which causes endothelial injury followed by platelet adhesion and aggregation at the site of photochemical reaction. Three weeks after endothelial injury, intimal thickening occurred at the irradiated site. Prostaglandin E₁ (0.3 μg/kg per min), administered as a continuous infusion 10 min before photochemical reaction significantly (P<0.05) prolonged the time to occlusion of the femoral artery. In a separate experiment, prostaglandin E₁ (0.3 μg/kg per min) administered as a continuous infusion for 7 days just after endothelial injury significantly (P<0.05) inhibited intimal thickening compared with a control group. In cultured rat-derived vascular smooth muscle cells, prostaglandin E₁ produced concentration-dependent inhibition of migration and proliferation, stimulated by platelet-derived growth factor. These results suggest that prostaglandin E₁ may be effective in preventing vascular restenosis after vascular surgery and angioplasty.     

Elevated plasma activator inhibitor 1 is not related to insulin resistance and to gene polymorphism in healthy centenarians

Previous studies demonstrated a relationship between the degree of insulin resistance and plasma plasminogen activator inhibitor type-1 (PAI-1) levels. We aim at investigating the relationship between the degree of insulin resistance and plasma PAI-1 levels in aged subjects (n=83) and in healthy centenarians (n=42). In all subjects the degree of insulin resistance was assessed by HOMA method. Our data demonstrated that healthy centenarians have higher plasma PAI-1 levels (73.1±13.9 vs 23.7±14.7 ng/ml, P<0.001) and lower degree of insulin resistance (1.4±0.5 vs 3.3±1.3, P<0.001) than aged subjects. In aged subjects plasma PAI-1 levels correlated with the degree of insulin resistance (r=0.61, P<0.001), fasting plasma triglycerides (r=0.74, P<0.001) and age (r=0.33, P<0.001). All such associations were lost in centenarians. Plasma PAI-1 Ag levels were also similar in aged subjects and centenarians even after categorization for PAI gene polymorphism. In multivariate analysis, a model made by age, sex, body mass index, fasting plasma triglycerides, HOMA and PAI-1 gene explained 65 and 50% of plasma PAI-1 level variations in aged subjects and centenarians, respectively. Nevertheless, HOMA (P<0.001) was significantly and independently associated with plasma PAI-1 levels only in aged subjects. In conclusion, our data demonstrates that in healthy centenarians, plasma PAI-1 were not associated with the degree of insulin resistance as in aged subjects. Frequency of PAI-1 genotype does not provide an explanation for such differences between aged subjects and centenarians.     

Postprandial cholesteryl ester transfer and high density lipoprotein composition in normotriglyceridemic non-insulin-dependent diabetic patients

Altered postprandial HDL metabolism is a possible cause of defective reverse cholesterol transport and increased cardiovascular risk in diabetic patients with a normal fasting lipoprotein profile. Ten normolipidemic, normoponderal non-insulin dependent diabetes mellitus (NIDDM) patients and seven controls received a 980 kcal meal containing 78 g lipids with 100000 IU vitamin A. Chylomicron clearance was not different, but area under the curve (AUC) for retinyl palmitate in chylimicron-free serum (remnant clearance) was greater in patients (P < 0.02). LCAT activity increased postprandially to the same extent in both groups. In control subjects, cholesteryl ester transfer protein (CETP) activity (CETA) also increased by 20% (P < 0.01 at 6 h) in parallel with a 20% decrease in HDL₂-CE (r= −0.55, P = 0.009). In NIDDM patients, on the contrary, CETA which was 35% higher in the fasting state (P < 0.005), decreased postprandially yet HDL₂-CE remained unchanged. Postprandial HDL₃ of controls were enriched with phospholipid (PL) (30.3 ± 2.6% at 6 h) with respect to fasting (25.6 ± 2.5%, P < 0.01) and to NIDDM-HDL₃ (25.8 ± 1.7% at 6 h, P < 0.01). These results show that variation in plasma CETA has little impact on HDL₂-CE in NIDDH subjects. They support the concept that, in controls, the combined enrichment of HDL₃ with PL, increased LCAT and CETA create the conditions for stimulation of cell cholesterol efflux and CE transfer to apo B lipoproteins. In NIDDM, because of the lesser HDL₃ enrichment with PL and of the inverse trend of CETA, these conditions fail to occur, depriving the patients of a potentially efficient mechanism of unesterified cholesterol (UC) clearance, despite their strictly normal preprandial profile.     

Effects of Momordica charantia fruit juice on islet morphology in the pancreas of the streptozotocin-diabetic rat

An investigation was made of the effect of Momordica charantia fruit juice on the distribution and number of , β and δ cells in the pancreas of streptozotocin (STZ)-induced diabetic rats using immunohistochemical methods. The results indicated that there was a significant (Student's t-test, P<0.004) increase in the number of β cells in M. charantia-treated animals when compared with untreated diabetics, however, their number was still significantly less than that obtained for normal rats. There was also a significant (P<0.006) increase in the number of δ cells in STZ-diabetic rats compared to non-diabetic rats. This increase in the number of δ cells was not affected by M. charantia treatment. The number of cells did not change significantly in M. charantia-treated rats when compared with untreated diabetic rats. Our results suggest that oral feeding of M. charantia fruit juice may have a role in the renewal of β cells in STZ-diabetic rats or alternately may permit the recovery of partially destroyed β cells.     

Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services

Objective: To determine whether cognitive impairment is associated with changes in self-care behaviour and use of health and social services in older subjects with diabetes mellitus. Research design and methods: This was a community based, case-control study of subjects registered with general practices participating in the All Wales Research into Elderly (AWARE) Diabetes Study. The 396 patients aged 65 years or older with known diabetes mellitus were compared with 393 age- and sex-matched, non-diabetic controls. Adjusted odds ratio estimates of normal performance on Mini-Mental State Examination (MMSE) and Clock Drawing Test (numbers and hands) were determined. Information on self-care behaviours and use of services was obtained. Results: A total of 283 (71%) diabetic subjects scored 24 or more on MMSE, compared with 323 (88%) of controls (OR 0.54, P<0.0005). The mean (S.D.) scores were 24.5 (5.1) and 25.7 (4.3), respectively (difference between means 1.22; 95% CI 0.56, 1.88; P<0.001). Clock testing demonstrated that 257 (65%) and 286 (72%) diabetic subjects correctly placed the numbers and hands, respectively, compared with 299 (76%) and 329 (84%) of controls (OR 0.59, P<0.001 and P<0.52, P<0.0005, respectively). Both test scores declined with increasing age, earlier school leaving age and deteriorating visual acuity. Of other variables examined, only need for oral hypoglycaemic drugs or insulin, history of stroke, dementia or Parkinson's disease and symptoms of autonomic neuropathy significantly impaired one or more cognitive test scores. The odds ratios (95% CI) for normal cognitive test results in subjects with diabetes after adjusting for all significant variables was 0.74 (0.56, 0.97), P=0.029 for MMSE scores and 0.63 (0.44, 0.93), P=0.019, and 0.58 (0.38, 0.89), P=0.013, for the numbers and hands parts of the clock test, respectively. In comparison with diabetic subjects with no evidence of cognitive impairment, diabetic subjects with an MMSE score <23 were significantly less likely to be involved in diabetes self-care (P<0.001) and diabetes monitoring (P<0.001). A low MMSE score was also significantly associated with higher hospitalisation in the previous year (P=0.001), reduced ADL (activities of daily living) ability (P<0.001) and increased need for assistance in personal care (P=0.001). Conclusions: Elderly subjects with predominantly Type 2 diabetes mellitus display significant excess of cognitive dysfunction, associated with poorer ability in diabetes self-care and greater dependency. Routine screening of cognition in older subjects with diabetes is recommended.     

Pulse waveform analysis of arterial compliance: relation to other techniques, age, and metabolic variables

T o assess the physiologic and clinical relevance of newer noninvasive measures of vascular compliance, computerized arterial pulse waveform analysis (CAPWA) of the radial pulse was used to calculate two components of compliance, C1 (capacitive) and C2 (oscillatory or reflective), in 87 normotensive (NlBP, n = 20), untreated hypertensive (HiBP, n = 21), and treated hypertensive (HiBP-Rx, n = 46) subjects. These values were compared with two other indices of compliance, the ratio of stroke volume to pulse pressure (SV/PP) and magnetic resonance imaging (MRI)–based aortic distensibility; and were also correlated with demographic and biochemical values.

The HiBP subjects displayed lower C1 (1.34 ± 0.09 v 1.70 ± 0.11 mL/mm Hg, significance [sig] = .05) and C2 (0.031 ± 0.003 v 0.073 ± 0.02 mL/mm Hg, sig = .005) than NlBP subjects. This was not true for C1 (1.64 ± 0.08 mL/mm Hg) and C2 (0.052 ± 0.005 mL/mm Hg) values in HiBP-Rx subjects. The C1 (r = 0.917, P < .0001) and C2 (r = 0.677, P < .0001) were both closely related to SV/PP, whereas C1 (r = 0.748, P = .002), but not C2, was significantly related to MRI-determined aortic distensibility.

Among other factors measured, age exerted a strong negative influence on both C1 (r = −0.696, P < .0001) and C2 (r = −0.611, P < .0001) compliance components. Positive correlations were observed between C1 (r = 0.863, P = .006), aortic distensibility (r = 0.597, P = .19) and 24-h urinary sodium excretion, and between C1- and MR spectroscopy-determined in situ skeletal muscle intracellular free magnesium (r = 0.827, P = .006), whereas C2 was inversely related to MRI-determined abdominal visceral fat area (r = −0.512, P = .042) and fasting blood glucose (r = −0.846, P = .001).

Altogether, the close correspondence between CAPWA, other compliance techniques, and known cardiovascular risk factors suggests the clinical relevance of CAPWA in the assessment of altered vascular function in hypertension.     

脊柱结核患者术后排气时间影响因素分析

目的: 探讨脊柱结核患者术后恢复排气时间的影响因素。 方法: 采用前瞻性横断面研究的方法,连续纳入2021年2—12月在首都医科大学附属北京胸科医院骨科新入住且符合入组标准的75例脊柱结核患者作为研究对象。使用病例报告表收集患者基本情况、入院次日和术后次日的血常规和血生化、手术方式、手术时长、疼痛处理、术后口渴评分、术后疼痛评分、术中出血量、术中输血量等指标,以及是否参加营养管理。采用单因素和多元逐步回归模型探讨影响脊柱结核患者恢复排气时间的潜在因素。 结果: 75例脊柱结核患者术后恢复排气的时间范围为0.5~98.0h,中位时间为27.0(19.0,40.0)h,≤24h者仅29例(38.7%)。单因素分析显示,脊柱结核患者术后恢复排气时间与入院次日的血红蛋白水平[(124.1±17.2)g/L]呈负相关(r=-0.289,P=0.012),与术后2h时的口渴评分[5.0(4.0,6.0)分]呈正相关(r=0.258,P=0.025);与其他因素均无相关性,如与是否进行营养管理[26.0(16.0,38.0)h和30.8(21.3,45.3)h]和术后24h疼痛评分[4.0(3.0,6.0)分]均无相关性(Z=-1.915,P=0.056;r=0.171,P=0.143)。多元逐步回归分析显示,入院次日血红蛋白水平、术后24h疼痛评分和是否进行营养管理均是脊柱结核患者术后恢复排气时间的潜在影响因素,且术后恢复排气时间随着血红蛋白水平的升高、营养管理的完善而缩短,随术后24h疼痛评分的增加而延长(β=-0.349,P=0.002;β=3.143,P=0.003;β=-10.312,P=0.008)。 结论: 脊柱结核患者术后排气恢复时间较长,临床医护人员应关注入院时贫血、住院期间未进行全程营养管理,以及术后24h疼痛评分较高的患者。     

Relationships between fibrinogen and insulin resistance

A relationship between plasma fibrinogen levels and insulinemia, as well as the different parameters of the insulin resistance syndrome has been described. The aim of the present paper was to investigate whether plasma fibrinogen concentrations were linked to plasma insulin levels or to the degree of insulin resistance. For this purpose, 62 nondiabetic, nonhypertensive patients, 30 men and 32 women, with body mass indexes (BMIs) and ages ranging from 18.6 to 50.2 kg/m² and from 19 to 60 years, respectively, were studied. Insulin sensitivity was quantified by the minimal model procedure over a 180-min intravenous glucose tolerance test with iterative sampling. Plasma insulin was determined by radioimmunoassay without cross-reactivity to human proinsulin, and fibrinogen by the method of Clauss. Insulin sensitivity ranged from 0.009 to 23.2 min⁻¹/(μU/ml)×10⁻⁴, covering the whole range of insulin sensitivities. Fibrinogen ranged from 1.70 to 5.07 g/l. There was a significant negative correlation between fibrinogen and insulin sensitivity (r=−0.76, P<0.0001) and a positive correlation between fibrinogen and basal insulin (r=0.56, P<0.0001). After adjustment for BMI, body fat mass and waist-to-hip ratio, these two relationships remained significant. In addition, a multiple regression analysis was performed to assess the independent effect of the following related variables: fibrinogen, insulin sensitivity, insulinemia and BMI. Only insulin sensitivity appeared to account for the ability to predict fibrinogen values. Thus, we hypothesized it was likely that the state of insulin resistance rather than hyperinsulinemia per se was related to hyperfibrinogenemia. We proposed an interpretation of these data in connection with some factors like free fatty acids or tumor necrosis factor-, which have been implicated in the pathogenesis of insulin resistance. Nevertheless, prospective and intervention studies are needed to assess whether there is a simple association or a causal relationship between insulin resistance and hyperfibrinogenemia.