Hyposomatotropism blunts lipolysis in abdominally obese women

Abdominal obesity is associated with reduced 24-h plasma GH concentrations. It is unclear whether hyposomatotropism in abdominally obese humans is compensated by up-regulation of GH receptor sensitivity or causes less biological effect in target tissues. We, therefore, determined the responsiveness of adipose tissue to the lipolytic action of GH in abdominally obese (OB) and normal weight (NW) postmenopausal women. An iv bolus of recombinant human GH or placebo was randomly administered to eight NW [body mass index (BMI): 22.2 +/- 1.6 kg/m(2)] and eight abdominally OB (BMI: 32.1 +/- 2.6 kg/m(2)) women. Lipolysis was measured by infusion of D5-glycerol and modeled as a function of plasma GH concentrations to describe adipose tissue responsiveness. Similar plasma GH concentration peaks ( approximately 20 mU/liter) were achieved by GH injection in both groups. During placebo conditions, the average plasma GH level was significantly lower in OB compared with NW women (0.74 +/- 0.52 vs. 2.08 +/- 1.18 mU/liter, P = 0.023). Adipose tissue responsiveness, expressed as glycerol rate of appearance per kilogram of fat mass per unit plasma GH concentration was not different in both groups (NW: 1.06, OB: 0.68, P > 0.05). These results suggest that hyposomatotropism in abdominally obese individuals is not compensated by increased adipose tissue responsiveness to GH bio-action and, therefore, blunts lipolysis in these individuals.     

A low-fat diet has a higher potential than energy restriction to improve high-fat diet-induced insulin resistance in mice

Previous studies have shown that energy restriction (ER) or low-fat (LF) diets have beneficial effects on high-fat (HF) diet-induced obesity and non-insulin-dependent diabetes. However, comparison between ER and low-fat diet regarding the effect on insulin resistance and lipid metabolism has not been reported. After inducing insulin resistance by HF feeding for 20 weeks, male C57BL/6J mice were divided into 3 groups. For a period of 12 weeks, group 1 received energy restriction (70% of ad libitum, HF diet), group 2 LF diet, and group 3 maintained on HF diet. Body weight and energy intake were reduced equally in ER and LF feeding. Plasma insulin levels were decreased on LF feeding, but were unchanged on ER, when compared with HF feeding. Glucose tolerance and insulin sensitivity tests revealed that insulin sensitivity was improved more efficiently by LF feeding than on ER. Plasma triglyceride (TG) levels were lower on LF feeding compared with ER and HF feeding. Measurement of hepatic very low-density lipoprotein (VLDL)-TG production revealed a lower production after LF diet feeding or ER compared with HF diet feeding. In summary, our data show that LF diet has a higher potential than ER to improve HF diet-induced insulin resistance, and that there is an association between improvement of insulin resistance and decrease of TG levels.     

Diagnosing genital ulcer disease in a clinic for sexually transmitted diseases in Amsterdam, The Netherlands

The most common etiologic agents of genital ulcer disease (GUD) are herpes simplex virus type 1 (HSV-1), HSV-2, Treponema pallidum, and Haemophilus ducreyi. In an outpatient clinic for sexually transmitted diseases in Amsterdam, The Netherlands, specimens from 372 patients with GUD were collected from February to November 1996. Sera were collected at the time of the symptoms and, for most patients, also during follow-up visits. Swabs in viral transport medium were used for HSV culture and for detection of DNA. The most prevalent pathogen found was HSV-2, which was detected by culture in 35% of the patients and by PCR in 48% of the patients. Also, HSV-1 infection was more often detected by PCR (7.8%) than by culture (5.6%). Evidence for an active infection with T. pallidum was found in 1.9% of the patients, using serological tests. A multiplex PCR for simultaneous T. pallidum and H. ducreyi DNA detection was positive for T. pallidum in 3.3% of the samples and for H. ducreyi in only 0.9% (3 out of 368) of the samples. The sensitivity of the PCR was superior to that of culture for HSV detection and to that of serology for T. pallidum detection. Specific H. ducreyi immunoglobulin G antibodies were detected in sera of 5.2% of the patients, with no concordance between serology and PCR. In 37% of the cases, none of the tested microorganisms was detected. Performance of PCR in addition to conventional techniques significantly improved the diagnosis of GUD.     

Insulin secretion and sensitivity after simultaneous pancreas-kidney transplantation estimated by continuous infusion of glucose with model assessment

BACKGROUND: Monitoring of insulin secretion and sensitivity after pancreas transplantation remains a practical problem. METHODS: We introduced the simple structural model, continuous infusion of glucose with model assessment (CIGMA), to obtain insulin secretion and insulin sensitivity estimations after 35 successful simultaneous pancreas-kidney transplantations. Eighteen non-diabetic kidney transplant recipients were used as control group. RESULTS: The baseline characteristics were equal between the two groups except for higher fasting insulin levels in the pancreas transplant group. After the 1-hr CIGMA glucose load, the pancreas transplant group reached a mean +/- SD blood glucose of 8.2+/-1.7 mmol/L compared with 7.3+/-1.0 mmol/L in the control group (P = 0.05). Concurrent stimulated insulin and C-peptide levels were 48+/-28 mU/L and 2.3+/-0.9 nmol/L in the pancreas transplant group compared with 36+/-21 mU/L and 2.9+/-1.1 nmol/L in the control group (P = 0.1 and P = 0.03, respectively). Both the CIGMA estimation for secretion as well as the CIGMA estimation for sensitivity were lower in pancreas transplant group (P = 0.003 and P = 0.01, respectively). Mean +/- SE coefficients of variation for the model estimations were 15+/-4% for secretion and 17+/-6% for sensitivity. CONCLUSIONS: We conclude that CIGMA can be used clinically to evaluate carbohydrate metabolism in pancreas-kidney transplant recipients. These patients have a reduction in insulin secretory capacity and evidence of more insulin resistance than non-diabetic kidney transplant recipients.     

Resting‐state and task‐based centrality of dorsolateral prefrontal cortex predict resilience to 1 Hz repetitive transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is used to investigate normal brain function in healthy participants and as a treatment for brain disorders. Various subject factors can influence individual response to rTMS, including brain network properties. A previous study by our group showed that “virtually lesioning” the left dorsolateral prefrontal cortex (dlPFC; important for cognitive flexibility) using 1 Hz rTMS reduced performance on a set‐shifting task. We aimed to determine whether this behavioural response was related to topological features of pre‐TMS resting‐state and task‐based functional networks. 1 Hz (inhibitory) rTMS was applied to the left dlPFC in 16 healthy participants, and to the vertex in 17 participants as a control condition. Participants performed a set‐shifting task during fMRI at baseline and directly after a single rTMS session 1–2 weeks later. Functional network topology measures were calculated from resting‐state and task‐based fMRI scans using graph theoretical analysis. The dlPFC‐stimulated group, but not the vertex group, showed reduced setshifting performance after rTMS, associated with lower task‐based betweenness centrality (BC) of the dlPFC at baseline (p = .030) and a smaller reduction in task‐based BC after rTMS (p = .024). Reduced repeat trial accuracy after rTMS was associated with higher baseline resting state node strength of the dlPFC (p = .017). Our results suggest that behavioural response to 1 Hz rTMS to the dlPFC is dependent on baseline functional network features. Individuals with more globally integrated stimulated regions show greater resilience to rTMS effects, while individuals with more locally well‐connected regions show greater vulnerability.     

Delayed onset of the diurnal melatonin rise in patients with Huntington’s disease

Sleep disturbances are very prevalent in Huntington’s disease (HD) patients and can substantially impair their quality of life. Accumulating evidence suggests considerable dysfunction of the hypothalamic suprachiasmatic nucleus (SCN), the biological clock, in both HD patients and transgenic mouse models of the disease. As melatonin has a major role in the regulation of sleep and other cyclical bodily activities and its synthesis is directly regulated by the SCN, we postulated that disturbed SCN function is likely to give rise to abnormal melatonin secretion in HD. Therefore, we compared 24 h melatonin secretion profiles between early stage HD patients and age-, sex- and body mass index-matched controls. Although mean diurnal melatonin levels were not different between the two groups (p = 0.691), the timing of the evening rise in melatonin levels was significantly delayed by more than 01:30 h in HD patients (p = 0.048). Moreover, diurnal melatonin levels strongly correlated with both motor (r = ?0.70, p = 0.036) and functional impairment (r = +0.78, p = 0.013). These findings suggest a delayed sleep phase syndrome-like circadian rhythm disorder in early stage HD patients and suggest that melatonin levels may progressively decline with advancing disease.     

Effect of tumour necrosis factor and lipid A on functional and structural vascular volume in solid murine tumours.

Effects of recombinant tumour necrosis factor (TNF) on functional and structural vascular volumes in solid murine Meth A tumours were investigated by injection of Hoechst 33342 and staining for the vascular basement membrane component laminin, respectively. Systemic injection of 3 x 10(4) U TNF caused an initial increase in functional volume in the tumour, but a strong decrease from 1 to 48 h after treatment. Early effects of intralesional treatment were more moderate. Systemic injection of 10(4) U TNF or 0.3 or 3 micrograms lipid A caused a fall in functional volume at 4 h, but a recovery was seen at 24 h. This recovery did not occur after treatment with a combination of 10(4) U TNF and 0.3 micrograms lipid A. Structural vascular volume was not markedly reduced until 24 h after treatment with the high doses of the separate agents and the combination. All effects appeared generally more prominent in the tumour centre than in the borders. Data suggest that TNF induces initially an active hyperaemia that rapidly converts to passive hyperaemia. A prolonged disturbance of tumour blood supply is probably necessary for therapeutic activity. Breakdown of laminin in the vascular basement membrane may be a cause of loss of vascular integrity.     

Effects of recombinant human leptin treatment as an adjunct of moderate energy restriction on body weight,resting energy expenditure and energy intake in obese humans

We explored the effects of recombinant human leptin (rL) as an adjunct of mild energy restriction (2092 kJ/day less than needed) in the treatment of obese humans as part of a larger multicentre trial. In a double blind, randomised, placebo (P)-controlled design, the effects of 10 mg of rL once daily vs twice daily (rL OD/BID, by s.c. injection) upon body weight, resting energy expenditure (REE) and energy intake were compared. The study groups comprised 9 (P), 15 (rL OD) and 6 (rL BID) healthy subjects (body mass index 27.5-35 kg/m2). We observed in both groups treated with rL a decline of body weight. [2.8+/-1.1 kg (P), 5.2+/-0.9 kg (rL OD), 7.9+/-1.4 kg (rL BID), p < 0.035]. No significant effects of rL treatment upon energy intake or REE were observed. However, rL tended to reduce the decline of energy expenditure associated with energy restriction, whereas the tendency of energy intake to increase back to baseline levels in placebo-treated subjects was largely prevented in subjects treated with rL. Thus, rL appears to enhance the loss of body weight in obese humans in a dose-dependent fashion if prescribed as an adjunct of energy restriction. This effect might be mediated by rL ability to counteract the behavioural and metabolic adaptations that accompany weight loss attempts.