Peripheral circulatory effects of insulin in diabetes

Peripheral circulatory effects of insulin were studied in the diabetic patients with and without autonomic neuropathy. Forearm blood flow, calf venous volume and calf venous distensibility were measured by strain gauge plethysmography. In the diabetic patients with autonomic neuropathy, mean blood pressure fell from 96 +/- 5 to 88 +/- 5 mmHg after an intravenous injection of 4 U of monocomponent insulin (p less than 0.001). Forearm vascular resistance decreased from 53.99 +/- 8.29 to 45.88 +/- 7.76 mmHg X ml-1 X 100ml-1 X min-1 after insulin (p less than 0.01). Insulin increased calf venous volume from 1.20 +/- 0.19 to 2.23 +/- 0.44 ml/100ml (p less than 0.05) and calf venous distensibility from 0.039 +/- 0.004 to 0.082 +/- 0.016 ml/mmHg (p less than 0.05). In contrast, in the diabetic patients without autonomic neuropathy, there were no significant changes in the mean blood pressure, forearm vascular resistance, calf venous volume and calf venous distensibility. Symptoms of hypoglycaemia did not occur in any patient. These results suggest that insulin has a vasodilator action on both resistance and capacitance vessels, which may be one of the main factors in insulin-induced hypotension.     

The choice of amniotic fluid in metabolomics for the monitoring of fetus health

Amniotic fluid (AF) is a biological fluid in which metabolite transport is regulated by the placenta, the permeable skin, fetal lung egress and gastric fluid. During pregnancy, the composition of AF changes from similar to the interstitial fluid of the mother, to a more complex system, influenced by the fetus’s urine. Since AF reflects the mother’s and the fetus’s health status at the same time, it may be an important diagnostic tool for a wider spectrum of clinical conditions. Indeed, the metabolic characterization of AF in relation to pathological occurrences may lead to the discovery of new biomarkers for a better clinical practice. For this reason, metabolomics may be the most suitable strategy for this task. In this review, research works on metabolomic AF analysis are discussed according to the morbidity of interest, being preterm birth/labor, gestational age and diabetes and fetal malformations, along with a number of other important studies.     

Substantially increased risk of cancer in patients with diabetes mellitus: A systematic review and meta-analysis of epidemiologic evidence in Japan

AimsSeveral meta-analyses have shown that diabetes mellitus affects the risk of certain site-specific cancers. However, a meta-analysis on the overall risk of cancer has not yet been performed.MethodsWe performed a search of MEDLINE and the Cochrane Library for pertinent articles (including their references) that had been published as of June 10, 2010. English-language, original observational cohort studies and case-control studies conducted in Japan were included for a qualitative review and a meta-analysis.ResultsA total of 22,485 cancer cases were reported in four cohort studies and one case-control study (with a total of 250,479 subjects). With these five reports, a meta-analysis of the all-cancer risk in both men and women showed an increased risk in subjects with diabetes, compared with nondiabetic subjects (OR 1.70, 95% CI 1.38–2.10). The increase in the risk ratio adjusted for possible confounders was significant in men and borderline in women (adjusted RR 1.25, 95% CI 1.06–1.46 in men; adjusted RR 1.23, 95% CI 0.97–1.56 in women). An analysis of site-specific cancers revealed increased risks for incident hepatocellular cancer (OR 3.64, 95% CI 2.61–5.07) and endometrial cancer (OR 3.43, 95% CI 1.53–7.72).ConclusionsAs is the case in Western countries, Asian people with diabetes have a higher risk of incident cancer than those without diabetes. Cancer prevention and early detection should be important components of diabetes management in light of the exponentially increasing prevalence of diabetes, which has substantial implications in public health and clinical practices.     

Leg massage therapy promotes psychological relaxation and reinforces the first-line host defense in cancer patients

Purpose

Patients with cancer suffer a wide range of physical symptoms coupled with psychological stress. Moreover, cancer chemotherapy induces immunosuppression and consequently causes respiratory infections. Massage therapy has been reported to reduce symptoms in cancer patients via an increase in psychosocial relaxation and to enhance and/or improve immune function.

Methods

In the present study, we determined whether leg massage could induce psychosocial relaxation and activate the first line of the host defense system. To assess effects of rest and leg massage, 15 healthy volunteers rested on a bed for 20 min on the first day, and 3 days later the subjects received a standardized massage of the legs for 20 min with nonaromatic oil. Twenty-nine cancer patients also received the same standardized massage of the legs. Anxiety/stress was assessed before and just after the rest or the massage using the State-Trait Anxiety Inventory (STAI-s) and visual analogue scale (VAS). To evaluate oral immune function, salivary chromogranin A (CgA) and secretory immunoglobulin A (sIgA) levels were measured.

Results

In healthy volunteers, rest significantly reduced VAS by 34% and increased sIgA by 61%. In contrast, leg massage significantly reduced both STAI-s and VAS by 24% and 63%, and increased both sIgA and CgA by 104% and 90%, respectively. In cancer patients, leg massage significantly decreased both STAI-s and VAS by 16% and 38%, and increased both salivary CgA and sIgA by 33% and 35%, respectively.

Conclusion

Leg massage may promote psychosocial relaxation and reinforce a first-line host defense with an increase in secretion of antimicrobial peptides.     

How does long-term parenteral nutrition impact the bone mineral status of children with intestinal failure?

Patients on long-term parenteral nutrition (PN) are at significantly increased risk for the development of metabolic bone disease (MBD); this condition is characterized by incomplete mineralization of osteoid with consequent disturbances ranging from osteopenia to severe bone disease with fractures. The aim of the study was: (1) to evaluate the prevalence of MBD, (2) to identify the PN- or intestinal failure (IF)-related factors and (3) to assess annual changes of bone mineral status. Since September 2005 all patients affected by IF and treated with PN started a BMD evaluation program using dual-energy X-ray absorptiometry (DXA). Twenty-four IF patients were included [15 with short bowel syndrome (SBS), 5 with severe protracted diarrhea and 4 with chronic intestinal pseudostruction]. The bone mineral density (BMD) Z-score was significantly lower in patients than in the control group. In our series SBS patients showed a BMD Z-score significantly higher in comparison with the medical causes of IF. No significant correlations were found between bone mineral status and PN duration and nutrient intake. Nine IF patients were submitted to a second DXA evaluation after 1 year from the baseline. All bone mineral variables were significantly increased at the second DXA evaluation. The high prevalence of MBD in IF patients undergoing long-term treatment with PN requires that these patients undergo careful and periodic monitoring of their bone mineral status; patients with congenital gut dysfunctions, such as epithelium defects and motility anomalies, are at major risk of developing this complication, probably due to the association with extra-intestinal causes of bone loss.     

Molecular diagnosis of hypobetalipoproteinemia: an ENID review

Primary hypobetalipoproteinemia (HBL) includes a group of genetic disorders: abetalipoproteinemia (ABL) and chylomicron retention disease (CRD), with a recessive transmission, and familial hypobetalipoproteinemia (FHBL) with a co-dominant transmission. ABL and CRD are rare disorders due to mutations in the MTP and SARA2 genes, respectively. Heterozygous FHBL is much more frequent. FHBL subjects often have fatty liver and, less frequently, intestinal fat malabsorption. FHBL may be linked or not to the APOB gene. Most mutations in APOB gene cause the formation of truncated forms of apoB which may or may be not secreted into the plasma. Truncated apoBs with a size below that of apoB-30 are not detectable in plasma; they are more frequent in patients with the most severe phenotype. Only a single amino acid substitution (R463W) has been reported as the cause of FHBL. Approximately 50% of FHBL subjects are carriers of pathogenic mutations in APOB gene; therefore, a large proportion of FHBL subjects have no apoB gene mutations or are carriers of rare amino acid substitutions in apoB with unknown effect. In some kindred FHBL is linked to a locus on chromosome 3 (3p21) but the candidate gene is unknown. Recently a FHBL plasma lipid phenotype was observed in carriers of mutations of the PCSK9 gene causing loss of function of the encoded protein, a proprotein convertase which regulates LDL-receptor number in the liver. Inactivation of this enzyme is associated with an increased LDL uptake and hypobetalipoproteinemia. HBL carriers of PCSK9 mutations do not develop fatty liver disease.     

Dietary conjugated linoleic acid preserves pancreatic function and reduces inflammatory markers in obese, insulin-resistant rats

Pancreatic preservation is an important part of diabetes management that may occur with improved peripheral insulin sensitivity and attenuated low-grade adipose tissue inflammation. The objective of the current study was to determine the response of obese, insulin-resistant fa/fa Zucker rats vs lean controls to dietary conjugated linoleic acid (CLA) supplementation with respect to pancreatic islet size, insulin resistance, and markers of inflammation and adipose glucose uptake. Six-week-old fa/fa and lean Zucker rats (n = 20 per genotype) were fed either a 1.5% CLA mixture or control diet for 8 weeks. Oral glucose tolerance testing was conducted at 7.5 weeks. Fasting serum haptoglobin, insulin, and C-peptide were assayed, and select messenger RNA (mRNA) and protein markers of inflammation and glucose metabolism were measured in adipose and liver tissues. CLA-fed fa/fa Zucker rats had smaller islet cell size, improved oral glucose tolerance and insulinemia, and attenuated serum haptoglobin levels compared with control-fed fa/fa Zucker rats, despite no differences in body weight and a slightly higher visceral adipose mass. CLA did not alter insulin sensitivity or islet size in lean Zucker rats. The CLA-fed fa/fa rats also had greater adipose glucose transporter-4 mRNA and less adipose tumor necrosis factor alpha mRNA and protein compared with control-fed fa/fa rats. In contrast, other markers of inflammation and glucose metabolism including adipose macrophage inflammatory factor, macrophage inflammatory protein-2, and liver pyruvate carboxylase and pyruvate dehydrogenase kinase 4 were not significantly changed. These results suggest that CLA supplementation preserved pancreatic function in conjunction with improved peripheral glucose use and reduced inflammation in fa/fa Zucker rats.     

Survival of breast cancer patients. Our experience

Life expectancy for patients with breast carcinoma has changed in Europe over the last two decades. In Italy, the overall survival rate is about 77% at 5 years. When considering the situation in Sicily, the EUROCARE 2 study examined survival data from the Ragusa Cancer Registry, showing that the curves are worse than in other regions of Italy. Starting from these considerations we decide to evaluate whether these data from the Ragusa Cancer Registry corresponded to Palermo data. So we analysed data from 575 consecutive patients with breast cancer, treated in our Breast Unit from 1990 to 2003 according to the St. Gallen Recommendations and followed for a median period of 5 years. The prognostic role of age, tumour size, nodal status, TNM, stage, grading and hormonal receptors (OR, PR) were analysed and survival curves at 5 and 10 years were produced using the actuarial survival methods. All causes of death were considered. The median follow-up was 33 months. The Log rank test and univariate cox proportional model were used to demonstrate the association between prognostic factors and outcome. When considering T and N status, the curves showed an inverse correlation between survival and increases in these parameters. Overall survival was 92.9% at 5 years and 81.4% at 10 years for T1, 78.4% at 5 years and 61.4% at 10 years for T2 and 40.8% for T3-T4 at 5 and 10 years. Overall survival for NO was 92.1% and 78.2%, respectively, at 5 and 10 years, but decreased to 72.0% and 59.9% at 5 and 10 years for N1. In N2 patients we found that only about 50% of patients were still alive at 5 and 10 years, while for N3 patients the figures were 57.2% and 40%, respectively.     

Topical Canrenoic Acid

The topical antiandrogenic activity of potassium canrenoate (CAK), compared with that of spironolactone (SP), was assayed in vivo in female golden Syrian hamsters whose flank organs were stimulated by subcutaneous administration of testosterone propionate. Sebaceous glands and hair were measured by a computerized image analyzer. Pigmented spots, sebaceous gland areas, and the diameter of hairs of the treated flank organs were smaller in the groups that received CAK (1.6 mg/day) and SP (0.4 mg/day). The authors' results showed that CAK may act as a topical antiandrogen on the hamster flank organ when applied in concentrations four times greater than the minimal active dosage of SP. Potassium canrenoate may be a useful weak topical antiandrogen, and it could be used in androgen-related skin disorders involving both sebaceous glands and hair, especially in men. These concentrations could be verified by additional clinical investigations.     

Correlation between salivary alpha-amylase activity and pain scale in patients with chronic pain

BACKGROUND AND OBJECTIVES: The visual analog scale (VAS) is commonly used to assess pain intensity. However, the VAS is of limited value if patients fail to reliably report. Objective assessments are therefore clearly preferable. Previous reports suggest that elevated salivary alpha-amylase may reflect increased physical stress. There is a close association between salivary alpha-amylase and plasma norepinephrine under stressful physical conditions. In this study, we have determined the usefulness of a portable salivary alpha-amylase analyzer as an objective biomarker of stress. METHODS: Thirty patients (male/female = 15/15, age: 60.5 +/- 15.3 years) with chronic low back or leg pain (pain (+) group) and 20 pain-free control patients undergoing elective surgery under general anesthesia with epidural analgesia (pain (-) group) were recruited. Patients received epidural block with 5 to 10 mL 1% lidocaine. VAS, blood pressure, and heart rates were assessed before and 30 and 45 minutes after the epidural block. Salivary alpha-amylase was simultaneously measured using a portable analyzer. The relationship between the VAS and salivary alpha-amylase in chronic pain patients was assessed. RESULTS: After the epidural block both heart rate and systolic blood pressure decreased by approximately 8%. In the pain (+) group, the epidural block markedly decreased the VAS pain scale and salivary alpha-amylase from 56 +/- 22 to 19 +/- 16 mm (P < .01) and from 82 +/- 48 to 45 +/- 28 U/mL (P < .01), respectively, with a significant correlation between the 2 measures (r = 0.561, P < .01). In contrast, salivary alpha-amylase did not change significantly in the pain (-) group. CONCLUSIONS: Because there was a significant correlation between VAS pain scale and salivary alpha-amylase, we suggest that this biomarker may be a good index for the objective assessment of pain intensity. In addition, a simple to use portable analyzer may be useful for such assessment.