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Biomedical subjects

Marco Castagneto

Publications and source records attributed to Marco Castagneto.

At least 19 recordsLinked to original sources
PubMed2006

Effect of massive weight loss on inflammatory adipocytokines and the innate immune system in morbidly obese women.

CONTEXT: Obesity may be regarded as a low-grade inflammatory state. OBJECTIVE: The aim of this study was to evaluate changes in pro-inflammatory adipocytokines and the innate immune system, cardiovascular risk, and insulin sensitivity after massive weight loss. DESIGN: This was a longitudinal study. SETTING: The study was conducted at Catholic University, Rome. SUBJECTS AND METHODS: There were 10 normoglucose-tolerant obese women evaluated before and 36 months after bilio-pancreatic diversion (BPD). Glucose sensitivity (M value) was estimated using the euglycemic-hyperinsulinemic clamp. Mannan-binding lectin (MBL), bactericidal/permeability increasing protein (BPI), alpha-defensins, soluble CD14 receptor (sCD14), C-reactive protein, adiponectin, leptin, visfatin, IL-6, and TNF-alpha were assayed. RESULTS: After massive weight loss (53% of excess body weight), leptin (P <or= 0.0001), IL-6 (P <or= 0.0001), alpha-defensins (P <or= 0.001), and C-reactive protein (P <or= 0.0001) decreased significantly. Adiponectin increased significantly (P <or= 0.001). Of the nine subjects who lost more than 20% of body mass index, sCD14 (2.87 +/- 0.5 to 2.55 +/- 0.5; P = 0.016) and visfatin levels (12.20 +/- 0.93 to 10.63 +/- 1.93 ng/ml; P = 0.045) decreased significantly. No significant changes were observed in TNF-alpha, BPI, or MBL. Insulin sensitivity more than doubled after BPD (P <or= 0.0001). sCD14 changes were significantly associated with body mass index (r0 = 0.80; P = 0.003) and M changes (r0 = -0.59; P = 0.03). MBL correlated with insulin sensitivity in obese (r0 = 0.93; P = 0.0001) and post-BPD women (r(0) = 0.66; P = 0.038). Adiponectin correlated negatively with cardiovascular risk (r0 = -0.709; P = 0.02) and IL-6 (r0 = -0.634; P = 0.05). Multiple linear regression analysis showed that changes in sCD14 were also significantly related to changes in insulin sensitivity. CONCLUSIONS: Surgically induced weight loss is capable of reversing low-grade inflammation, at least partially. The relationships between sCD14, MBL, BPI, and glucose sensitivity, and the role of TNF-alpha in obesity warrant further investigation.

Acute-Phase Reaction↗
PubMed2006

Ultradian ghrelin pulsatility is disrupted in morbidly obese subjects after weight loss induced by malabsorptive bariatric surgery.

BACKGROUND: Suppression of ghrelin production after Roux-en-Y gastric bypass that suggested its contribution to appetite reduction has been reported. OBJECTIVE: Because biliopancreatic diversion (BPD) does not affect appetite, we compared ghrelin production and 24-h pulsatility between healthy control subjects and obese subjects before and after BPD. DESIGN: A computerized algorithm identified peak heights, clearance rate, and peak frequency of ghrelin over 24 h. Twenty-four-hour energy expenditure was measured in the calorimetric chamber, and energy intakes were computed. Insulin sensitivity was measured with a euglycemic-hyperinsulinemic clamp. RESULTS: Mean (+/-SD) 24-h plasma ghrelin concentrations were significantly (P < 0.0001) higher in control than in obese subjects (338.17 +/- 22.09 and 164.47 +/- 29.19 microg/L, respectively), but they increased to 204.64 +/- 28.51 microg/L in the obese subjects after BPD (P < 0.01). The pulsatility index was 0.098 +/- 0.016 and 0.041 +/- 0.014 microg . L(-1) . min(-1) in control and obese subjects, respectively (P < 0.01), and decreased to 0.025 +/- 0.007 microg . l(-1) . min(-1) after BPD (P < 0.05). Energy intakes before and after BFP did not differ significantly. Although metabolizable energy after BPD was 40% of the energy intake, that (per kg fat-free mass) after BPD did not different significantly from that before BPD. CONCLUSIONS: Weight loss induced by malabsorptive bariatric surgery is associated with greater ghrelin concentrations, which, however, remain consistently lower than those in control subjects, whereas ghrelin pulsatility is subverted. Higher ghrelin concentrations may contribute to the high calorie intakes observed in post-BPD subjects. The lack of normal pulsatility may explain the new impulse of these subjects to eat very frequently.

Activity Cycles↗
PubMed2006

The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes.

SUMMARY BACKGROUND DATA: Most patients who undergo Roux-en-Y gastric bypass (RYGB) experience rapid resolution of type 2 diabetes. Prior studies indicate that this results from more than gastric restriction and weight loss, implicating the rearranged intestine as a primary mediator. It is unclear, however, if diabetes improves because of enhanced delivery of nutrients to the distal intestine and increased secretion of hindgut signals that improve glucose homeostasis, or because of altered signals from the excluded segment of proximal intestine. We sought to distinguish between these two mechanisms. METHODS: Goto-Kakizaki (GK) type 2 diabetic rats underwent duodenal-jejunal bypass (DJB), a stomach-preserving RYGB that excludes the proximal intestine, or a gastrojejunostomy (GJ), which creates a shortcut for ingested nutrients without bypassing any intestine. Controls were pair-fed (PF) sham-operated and untreated GK rats. Rats that had undergone GJ were then reoperated to exclude the proximal intestine; and conversely, duodenal passage was restored in rats that had undergone DJB. Oral glucose tolerance (OGTT), food intake, body weight, and intestinal nutrient absorption were measured. RESULTS: There were no differences in food intake, body weight, or nutrient absorption among surgical groups. DJB-treated rats had markedly better oral glucose tolerance compared with all control groups as shown by lower peak and area-under-the-curve glucose values (P < 0.001 for both). GJ did not affect glucose homeostasis, but exclusion of duodenal nutrient passage in reoperated GJ rats significantly improved glucose tolerance. Conversely, restoration of duodenal passage in DJB rats reestablished impaired glucose tolerance. CONCLUSIONS: This study shows that bypassing a short segment of proximal intestine directly ameliorates type 2 diabetes, independently of effects on food intake, body weight, malabsorption, or nutrient delivery to the hindgut. These findings suggest that a proximal intestinal bypass could be considered for diabetes treatment and that potentially undiscovered factors from the proximal bowel might contribute to the pathophysiology of type 2 diabetes.

Animals↗
PubMed2006

Medium-chain, even-numbered dicarboxylic acids as novel energy substrates: an update.

Medium-chain dicarboxylic acids are produced by higher plants and animals via fatty acid omega-oxidation or by beta-oxidation of longer-chain dicarboxylic acids. In plants, dicarboxylic acids are components of the natural protective polymers cutin and suberin; in animals, dicarboxylic acids are mainly oxidized in mitochondria, where they are transported through four different pathways. Their energy density is intermediate between glucose and fatty acids. Dicarboxylic acid administration does not require insulin or stimulate insulin secretion, and the beta-oxidation of dicarboxylic acids produces succinic acid, a gluconeogenic substrate. Therefore, dicarboxylic acids might be a suitable fuel substrate, particularly in clinical conditions in which marked insulin resistance and/or impairment of aerobic glycolysis occur.

Animals↗
PubMed2006

Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery.

Currently, there are no data in the literature regarding the pathophysiological mechanisms involved in the rapid resolution of type 2 diabetes after bariatric surgery, which was reported as an additional benefit of the surgical treatment for morbid obesity. With this question in mind, insulin sensitivity, using euglycemic-hyperinsulinemic clamp, and insulin secretion, by the C-peptide deconvolution method after an oral glucose load, together with the circulating levels of intestinal incretins and adipocytokines, have been studied in 10 diabetic morbidly obese subjects before and shortly after biliopancreatic diversion (BPD) to avoid the weight loss interference. Diabetes disappeared 1 week after BPD, while insulin sensitivity (32.96 +/- 4.3 to 65.73 +/- 3.22 mumol . kg fat-free mass(-1) . min(-1) at 1 week and to 64.73 +/- 3.42 mumol . kg fat-free mass(-1) . min(-1) at 4 weeks; P < 0.0001) was fully normalized. Fasting insulin secretion rate (148.16 +/- 20.07 to 70.0.2 +/- 8.14 and 83.24 +/- 8.28 pmol/min per m(2); P < 0.01) and total insulin output (43.76 +/- 4.07 to 25.48 +/- 1.69 and 30.50 +/- 4.71 nmol/m(2); P < 0.05) dramatically decreased, while a significant improvement in beta-cell glucose sensitivity was observed. Both fasting and glucose-stimulated gastrointestinal polypeptide (13.40 +/- 1.99 to 6.58 +/- 1.72 pmol/l at 1 week and 5.83 +/- 0.80 pmol/l at 4 weeks) significantly (P < 0.001) decreased, while glucagon-like peptide 1 significantly increased (1.75 +/- 0.16 to 3.42 +/- 0.41 pmol/l at 1 week and 3.62 +/- 0.21 pmol/l at 4 weeks; P < 0.001). BPD determines a prompt reversibility of type 2 diabetes by normalizing peripheral insulin sensitivity and enhancing beta-cell sensitivity to glucose, these changes occurring very early after the operation. This operation may affect the enteroinsular axis function by diverting nutrients away from the proximal gastrointestinal tract and by delivering incompletely digested nutrients to the ileum.

Adiponectin↗
PubMed2005

Two corticosteroid-free regimens-tacrolimus monotherapy after basiliximab administration and tacrolimus/mycophenolate mofetil-in comparison with a standard triple regimen in renal transplantation: results of the Atlas study.

BACKGROUND: The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy. METHODS: This was a 6-month, phase III, open-label, parallel-group, multicenter study. The total analysis set comprised 451 patients, randomized (1:1:1) to receive tacrolimus (Tac) monotherapy following basiliximab (Bas) administration (n=153), Tac/mycophenolate mofetil (MMF) (n=151), or, Tac/MMF/corticosteroids triple therapy as a control (n=147). RESULTS: The study was completed by 91.2% (triple therapy), 94.7% (Tac/MMF), and 82.4% (Bas/Tac) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 8.2% (triple therapy), 30.5% (Tac/MMF), and 26.1% (Bas/Tac), p<0.001 (multiple test for comparison with triple therapy); Bas/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 2.0%, 4.0%, and 5.2%, p=ns. Graft survival (95.9%, 96.7%, and 94.7%, p=ns) and patient survival (100%, 99.3%, and 99.3%, p=ns) were similar in all groups. Median serum creatinine at month 6 was 123.0 micromol/L (triple therapy), 134.7 micromol/L (Tac/MMF) and 135.8 micromol/L (Bas/Tac). The overall safety profiles were similar; differences (p<0.05) were reported for anaemia (24.5% vs. 12.6% vs. 14.5%), diarrhoea (12.9% vs. 17.9% vs. 5.9%), and leukopenia (7.5% vs. 18.5% vs. 5.9%) for the triple therapy, Tac/MMF, and Bas/Tac group, respectively. The incidences of new-onset diabetes mellitus were 4.6%, 7.1%, and 1.4%, respectively. CONCLUSION: Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens. Both corticosteroid-free regimens were equally effective in preventing acute rejection, with the Bas/Tac therapy offering some safety benefits.

Adrenal Cortex Hormones↗
PubMed2005

Leptin pulsatility in formerly obese women.

Plasma leptin and growth hormone (GH) profile and pulsatility have been studied in morbidly obese subjects before and 14 months after bilio-pancreatic diversion (BPD), a bariatric technique producing massive lipid malabsorption. The maximum leptin diurnal variation (acrophase) decreased (10.27+/-1.70 vs. 22.60+/-2.79 ng x ml(-1); P=0.001), while its pulsatility index (PI) increased (1.084+/-0.005 vs. 1.050+/-0.004 ng x ml(-1) x min(-1); P=0.02) after BPD. Plasma GH acrophase increased (P=0.0001) from 0.91+/-0.20 to 4.58+/-0.80 microg x l(-1) x min(-1) after BPD as well as GH PI (1.70+/-0.13 vs. 1.20+/-0.04 microg x l(-1) x min(-1); P=0.024). Whole-body glucose uptake (M), assessed by euglycemic-hyperinsulinemic clamp, almost doubled after BPD (from 0.274+/-0.022 to 0.573+/-0.027 mmol x kgFFM(-1) x min(-1); P<0.0001), while 24 h lipid oxidation was significantly (P<0.0001) reduced (131.94+/-35.58 vs. 44.56+/-15.10 g). However, the average lipid oxidation was 97.2+/-3.1% (P<0.01) of the metabolizable lipid intake after the bariatric operation, while it was 69.2+/-8.5% before. After the operation, skeletal muscle ACC2 mRNA decreased (P<0.0001) from 452.82+/-76.35 to 182.45+/-40.69% of cyclophilin mRNA as did the malonyl-CoA (from 0.28+/-0.02 to 0.16+/-0.01 nmol x g(-1); P<0.0001). Leptin changes negatively correlated with M changes (R2=0.69, P<0.001). In a stepwise regression (R2=0.87, P=0.0055), only changes in 24 h free fatty acids (B=0.105+/-0.018, P=0.002) and glucose/insulin ratio (B=0.247+/-0.081, P=0.029) were the best predictors of leptin variations. In conclusion, the reversion of insulin resistance after BPD might allow reversal of leptin resistance, restoration of leptin pulsatility, and consequent inhibition of ACC2 mRNA expression, translating to a reduced synthesis of malonyl-CoA, which, in turn, results in increased fatty acid oxidation. Finally, since leptin inhibits GH secretion, a reduction of circulating leptin levels might have produced an increase in GH secretion, as observed in our series.

Acetyl-CoA Carboxylase↗
PubMed2005

Results of a three-year prospective study of C2 monitoring in long-term renal transplant recipients receiving cyclosporine microemulsion.

BACKGROUND: The clinical utility of C(2) monitoring of cyclosporine A microemulsion (CsA-ME) was evaluated in a prospective study of 110 patients more than 12 months posttransplant who demonstrated stable graft function and were receiving CsA-ME and steroids. METHODS: Patients were converted to C(2) monitoring with the CsA-ME dose adjusted to a target C(2) range of 800 to 1,000 ng/mL and followed for 40 + 11 months. RESULTS: At the time of conversion, 57% of patients exceeded the C(2) target, 20% of patients were below the C(2) target, and 23% of patients were within the C(2) target range. The mean dose of CsA-ME decreased from 258 + 88 to 202 + 76 mg/day (P < 0.0001), and the mean C(2) level decreased from 1,052 + 292 ng/mL to 896 + 233 ng/mL (P < 0.0002). There were no episodes of rejection. At last follow-up, 7.3% of patients had developed chronic renal allograft dysfunction. Use of antihypertensive agents decreased significantly (P = 0.0004), and mean total cholesterol decreased from 6.4 + 1.3 to 5.8 + 1.1 (P = 0.0009) after adoption of C(2) monitoring. CONCLUSION: These findings suggest that conversion of maintenance renal transplant recipients from C(0) to C(2) monitoring of CsA-ME offers the clinical benefits of better control of hypertension and dyslipidemia, with effective protection against chronic renal allograft dysfunction. A target C(2) range of 800 to 1,000 ng/mL in maintenance patients receiving CsA-ME dual therapy seems appropriate.

Adult↗
PubMed2005

Low 25-hydroxyvitamin D does not affect insulin sensitivity in obesity after bariatric surgery.

OBJECTIVE: A positive correlation between levels of 25-hydroxyvitamin D [25(OH)D] and insulin sensitivity has been shown in healthy subjects. We aimed to test the hypothesis that concentration of 25(OH)D influences insulin sensitivity in obesity before and after weight loss. RESEARCH METHODS AND PROCEDURES: We investigated the relation between serum 25(OH)D and insulin sensitivity (estimated by euglycemic-hyperinsulinemic clamp) in 116 obese women (BMI > or = 40 kg/m2) evaluated before and 5 and 10 years after biliopancreatic diversion (BPD). Body composition was estimated by the isotope dilution method. RESULTS: Prevalence of hypovitaminosis D was 76% in the obese status and 91% and 89% at 5 and 10 years after BPD, respectively, despite ergocalciferol supplementation. 25(OH)D concentration decreased from 39.2 +/- 22.3 in obesity (p = 0.0001) to 27.4 +/- 16.4 and 25.1 +/- 13.9 nM 5 and 10 years after BPD, respectively. Whole-body glucose uptake increased from 24.27 +/- 4.44 at the baseline to 57.29 +/- 11.56 and 57.71 +/- 8.41 mumol/kg(fat free mass) per minute 5 and 10 years after BPD, respectively (p = 0.0001). Predictor of 25(OH)D was fat mass (R2 = 0.26, p = 0.0001 in obesity; R2 = 0.20, p = 0.02 after BPD). Parathormone correlated with fat mass (R2 = 0.19; p = 0.0001) and BMI (R2 = 0.053; p = 0.01) and inversely with M value (R2 = 0.16; p = 0.0001), but only in obese subjects. DISCUSSION: A high prevalence of hypovitaminosis D was observed in morbid obesity both before and after BPD. Low 25(OH)D did not necessarily imply increased insulin resistance after BPD, a condition where, probably, more powerful determinants of insulin sensitivity overcome the low circulating 25(OH)D levels. However, the present data cannot exclude some kind of influence of vitamin D status on glucose and insulin metabolism.

Adult↗
PubMed2005

Changes in fat mass influence SREBP-1c and UCP-2 gene expression in formerly obese subjects.

OBJECTIVE: To investigate the effect of fat mass (FM) reduction on adipose tissue gene expression in terms of lipid synthesis [sterol regulatory binding protein 1c (SREBP-1c)] and lipid oxidation [uncoupling protein 2 (UCP-2)] 2 years after lipid malabsorption and to assess the influence of lipid malabsorption on fat-free mass (FFM) maintenance evaluating the expression of genes related to glycolysis [hexokinase (HKII)] and glucose storage [glycogen synthase (GS)]. RESEARCH METHOD AND PROCEDURES: SREBP-1c, UCP-2, HKII, and GS mRNA expression were studied by reverse transcriptase-competitive polymerase chain reaction in 10 massively obese subjects before and 2 years after bilio-pancreatic diversion (BPD). Body composition was assessed by isotopic dilution method and insulin sensitivity by euglycemic-hyperinsulinemic clamp. RESULTS: FM decrease was approximately 60%, whereas FFM remained at normal physiological levels. In adipose tissue, SREBP-1c mRNA reduction (-39%, p < 0.005) was related only to FM changes after BPD, and UCP-2 decrease (-37%, p < 0.05) was dependent on free fatty acid (FFA) changes. No significant variations were observed in HKII and GS gene expression in skeletal muscle. DISCUSSION: Lipid malabsorption induced by BPD altered the expression of genes involved in glucose and lipid metabolism, with different consequences on FM and FFM. The degree of FM loss seems to interfere with SREBP-1c gene suppression to preserve an adequate amount of fat storage, in accordance with the thrifty genotype hypothesis. The reduction of FFAs induced by BPD acts in inhibiting FFA transportation to the mitochondria (UCP-2), contributing to the decreased lipid oxidation inside the adipose tissue.

Adipose Tissue↗
PubMed2005

Predictors of weight loss and reversal of comorbidities in malabsorptive bariatric surgery.

BACKGROUND: Cardiovascular and metabolic comorbidities are dramatically increased in severe obesity, a condition highly resistant to nonsurgical therapy. OBJECTIVE: The objective was to identify predictors of weight loss and reversal of comorbidity in obese patients undergoing malabsorptive bariatric surgery. DESIGN: Morbidly obese men and women (n = 107) were studied before and 2 y after biliopancreatic diversion (BPD). Body composition, serum lipid profile, oral glucose tolerance, and blood pressure were measured. Insulin sensitivity was determined by use of a euglycemic clamp. The length of the small intestine was measured during surgery. RESULTS: Intestinal length was 671 +/- 99 cm, and the residual absorbing intestine after BPD ranged from 54% to 24% of initial length. Patients lost an average of 36% of their initial weight, with approximately 50% of them reaching a body mass index (in kg/m(2)) < 30. Serum cholesterol decreased (from 4.58 +/- 1.11 to 3.34 +/- 0.73 mmol/L; P < 0.0001), as did serum triacylglycerols (from 1.52 +/- 0.59 to 0.88 +/- 0.35 mmol/L; P < 0.0001), whereas insulin sensitivity rose 150% (from 26 +/- 4 to 64 +/- 11 micromol . min(-1) . kg fat-free mass(-1); P < 0.0001). Diabetes (in 23% of patients before surgery) and hypertension (in 83%) were reduced (by 88% and 96%, respectively) after surgery. In a multivariate model (including sex, age, intestinal length, presence of diabetes, insulin sensitivity, and initial fat mass), age and diabetes were independent, negative predictors of weight loss, whereas initial fat mass was a strong positive predictor (r(2) = 0.51). CONCLUSIONS: Two years after BPD in morbidly obese patients, comorbidities are largely corrected and insulin resistance is fully reversed despite persistent obesity. Initial fat mass, but not residual intestinal length, is the strongest predictor of weight loss after BPD.

Adipose Tissue↗
PubMed2005

Post-transplant diabetes mellitus: a case-control analysis of the risk factors.

Aim of the present study was to assess, in a pair-matched analysis design, risk factors for post-transplant diabetes mellitus (PTDM) in renal transplant recipients (KTx). The incidence of PTDM was evaluated in 538 consecutive KTx in relation to their baseline immunosuppression. PTDM was defined according to the 2003 American Diabetes Association and World Health Organization experts committee definition. As risk factors for PTDM development were considered: age, family history of diabetes, body mass index (BMI), baseline immunosuppression, doses and blood levels of the immunosuppressive agents used. Baseline immunosuppression consisted of CSA, TAC and SRL + CNI. Thirty-two pair-matched controls were identified among the 538 KTx and included in the risk analysis. Significant risk factors for the development of PTDM were identified in the family history of diabetes (P < 0.02) and BMI (P < 0.05). Higher BMI and positive family history for diabetes mellitus were significant risk factors for the development of PTDM, regardless of the immunosuppressive agent used.

Adult↗
PubMed2005

RGDS peptide inhibits activation of lymphocytes and adhesion of activated lymphocytes to human umbilical vein endothelial cells in vitro.

The Arg-Gly-Asp (RGD) motif is known to mediate cell adhesion to several extracellular matrix components as well as cell-cell interactions. In the present study, we investigated whether the RGDS peptide interferes with cell-cell recognition-based events such as allogeneic activation of PBMC and PBMC adhesion to human umbilical vein endothelial cells (HUVEC). We show here for the first time, to our knowledge, that RGDS significantly inhibits adhesion of activated PBMC to HUVEC; in addition, RGDS inhibits PBMC allogenenic activation in human mixed lymphocyte reaction assays. Caspases played a pivotal role in both events, because preventing their activation abolished or strongly reduced the observed inhibitory effect. The RGDS antirecognition effect was strongly increased by pretreatment of HUVEC with RGDS, which affected mostly T lymphocyte adhesion to HUVEC. These results indicate that PBMC allogeneic activation, as well as reciprocal recognition between activated PBMC and endothelial cells, are RGDS-dependent events that occur through a dual effect involving anti-adhesive and caspase-dependent mechanisms. These data suggest a potential role of RGDS in cell-mediated immunity, inflammation and organ transplantation.

Caspases↗
PubMed2005

Biliopancreatic diversion as a novel approach to the HAIR-AN syndrome.

BACKGROUND: The HAIR-AN syndrome is a rare multisystem disorder in women, that consists of hyperandrogenism (HA), insulin resistance (IR) and acanthosis nigricans (AN). The IR is likely due to a primary defect of the insulin receptor. METHODS: We report the case of a 42-year-old Caucasian woman with HAIR-AN syndrome, impaired glucose tolerance (IGT), mild hyperlipemia, and hypertension, who underwent biliopancreatic diversion (BPD). RESULTS: Within 24 months follow-up after BPD, impaired glucose tolerance, mild hyperlipemia, and hypertension completely reversed. Although insulin sensitivity, estimated by the euglycemic hyperinsulinemic clamp, did not improve, signs and symptoms of hyperandrogenism and acanthosis nigricans resolved fully. CONCLUSION: In HAIR-AN syndrome, malabsorptive bariatric surgery is effective in improving hyperandrogenism and acanthosis nigricans, with noteworthy esthetic consequences. BPD was followed by disappearance of co-morbidities of the syndrome, such as IGT, hypertension and hyperlipemia.

Acanthosis Nigricans↗
PubMed2005

Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6.

The primary gene mutated in Charcot-Marie-Tooth type 2A is mitofusin-2 (Mfn2). Mfn2 encodes a mitochondrial protein that participates in the maintenance of the mitochondrial network and that regulates mitochondrial metabolism and intracellular signaling. The potential for regulation of human Mfn2 gene expression in vivo is largely unknown. Based on the presence of mitochondrial dysfunction in insulin-resistant conditions, we have examined whether Mfn2 expression is dysregulated in skeletal muscle from obese or nonobese type 2 diabetic subjects, whether muscle Mfn2 expression is regulated by body weight loss, and the potential regulatory role of tumor necrosis factor (TNF)alpha or interleukin-6. We show that mRNA concentration of Mfn2 is decreased in skeletal muscle from both male and female obese subjects. Muscle Mfn2 expression was also reduced in lean or in obese type 2 diabetic patients. There was a strong negative correlation between the Mfn2 expression and the BMI in nondiabetic and type 2 diabetic subjects. A positive correlation between the Mfn2 expression and the insulin sensitivity was also detected in nondiabetic and type 2 diabetic subjects. To determine the effect of weight loss on Mfn2 mRNA expression, six morbidly obese subjects were subjected to weight loss by bilio-pancreatic diversion. Mean expression of muscle Mfn2 mRNA increased threefold after reduction in body weight, and a positive correlation between muscle Mfn2 expression and insulin sensitivity was again detected. In vitro experiments revealed an inhibitory effect of TNFalpha or interleukin-6 on Mfn2 expression in cultured cells. We conclude that body weight loss upregulates the expression of Mfn2 mRNA in skeletal muscle of obese humans, type 2 diabetes downregulates the expression of Mfn2 mRNA in skeletal muscle, Mfn2 expression in skeletal muscle is directly proportional to insulin sensitivity and is inversely proportional to the BMI, TNFalpha and interleukin-6 downregulate Mfn2 expression and may participate in the dysregulation of Mfn2 expression in obesity or type 2 diabetes, and the in vivo modulation of Mfn2 mRNA levels is an additional level of regulation for the control of muscle metabolism and could provide a molecular mechanism for alterations in mitochondrial function in obesity or type 2 diabetes.

Charcot-Marie-Tooth Disease↗
PubMed2004

Sirolimus-based therapy following early cyclosporine withdrawal provides significantly improved renal histology and function at 3 years.

Graft function and histology are predictive of renal transplant survival. The Rapamune Maintenance Regimen study demonstrated that early cyclosporine (CsA) withdrawal from a sirolimus (SRL)-CsA-steroid (ST) regimen improved renal function and blood pressure. We report the protocol-mandated biopsy findings from that study. Renal transplant patients (n = 430) receiving SRL-CsA-ST were randomized at 3 months after transplantation to remain on SRL-CsA-ST, or to have CsA withdrawn (SRL-ST group). Protocol-mandated biopsies were performed at engraftment and at 12 and 36 months. Two pathologists blindly evaluated 484 biopsies to obtain the Chronic Allograft Damage Index (CADI) scores. At 36 months among patients with serial biopsies (n = 63), the mean CADI score was significantly lower with SRL-ST(4.70 vs. 3.20, p = 0.003), as was the mean tubular atrophy score (0.77 vs. 0.32, p < 0.001). All six components of the CADI score were numerically lower in SRL-ST group; moreover, inflammation and the tubular atrophy scores decreased significantly in the SRL-ST group between 12 and 36 months. The calculated glomerular filtration rate at 36 months was significantly better in the CsA-withdrawal group (54.8 vs. 68.2 mL/min, p = 0.009). In conclusion, withdrawing CsA from the SRL-CsA-ST regimen resulted in improved renal histology and function.

Adult↗