Cucurbit[6]uril-Supported Fe3O4 Magnetic Nanoparticles Catalyzed Green and Sustainable Synthesis of 2-Substituted Benzimidazoles via Acceptorless Dehydrogenative Coupling.

A new composite, cucurbit[6]uril (CB[6])-supported magnetic nanoparticles, Fe3O4-CB[6], was synthesized via a co-precipitation method in air and fully characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction, X-ray photoelectron spectroscopy, field-emission scanning electron microscopy, high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, inductively coupled plasma-mass spectrometry, and vibrating sample magnetometry techniques. It has been found to be a highly efficient, economic, and sustainable heterogeneous catalyst and has been employed for the first time for the synthesis of a series of biologically important 2-substituted benzimidazoles from various benzyl alcohols and 1,2-diaminobenzenes under solvent-free conditions via acceptorless dehydrogenative coupling to afford the corresponding products in good to excellent yields (68-94%). The magnetic nature of the nanocomposite facilitates the facile recovery of the catalyst from the reaction mixture by an external magnet. The catalyst can be reused up to five times with negligible loss in its catalytic activity. All the isolated products were characterized by 1H and 13C{1H} NMR spectroscopy.

Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-blind clinical trial.

AIMS: To determine the blood glucose lowering effect of cinnamon on HbA1c, blood pressure and lipid profiles in people with type 2 diabetes. METHODS: 58 type 2 diabetic patients (25 males and 33 females), aged 54.9 ± 9.8, treated only with hypoglycemic agents and with an HbA1c more than 7% were randomly assigned to receive either 2g of cinnamon or placebo daily for 12 weeks. RESULTS: After intervention, the mean HbA1c was significantly decreased (P<0.005) in the cinnamon group (8.22% to 7.86%) compared with placebo group (8.55% to 8.68%). Mean systolic and diastolic blood pressures (SBP and DBP) were also significantly reduced (P<0.001) after 12 weeks in the cinnamon group (SBP: 132.6 to 129.2 mmHg and DBP: 85.2 to 80.2 mmHg) compared with the placebo group (SBP: 134.5 to 134.9 mmHg and DBP: 86.8 to 86.1 mmHg). A significant reduction in fasting plasma glucose (FPG), waist circumference and body mass index (BMI) was observed at week 12 compared to baseline in the cinnamon group, however, the changes were not significant when compared to placebo group. There were no significant differences in serum lipid profiles of total cholesterol, triglycerides, HDL and LDL cholesterols neither between nor within the groups. CONCLUSIONS: Intake of 2g of cinnamon for 12 weeks significantly reduces the HbA1c, SBP and DBP among poorly controlled type 2 diabetes patients. Cinnamon supplementation could be considered as an additional dietary supplement option to regulate blood glucose and blood pressure levels along with conventional medications to treat type 2 diabetes mellitus.

Effect of oral vitamin D and calcium replacement on glycaemic control in South Asian patients with type 2 diabetes.

BACKGROUND: Vitamin D deficiency is associated with a greater risk of developing type 2 diabetes mellitus (T2DM). Studies looking at the effect of vitamin D replacement on glycaemic control in type 2 diabetics are few and conflicting. In addition, none have been published looking at the South Asian population despite both T2DM and vitamin D deficiency being gross burdens in this population. The aim of this study was to determine the effect of using vitamin D and calcium replacement therapy on glycaemic control in South Asian patients with T2DM and vitamin D inadequacy. MATERIALS AND METHODS: Data were collected retrospectively from patients' records focusing on South Asians with established T2DM treated with combined oral vitamin D(3) and calcium supplementation. Vitamin D, parathyroid hormone (PTH), HbA1c and weight were recorded before and after 3 months on this therapy. RESULTS: Post-treatment, all patients' (n = 52) vitamin D levels were normalised (> 50nmol/l). There was a mean decrease in HbA1c of 0.70 +/- 0.77% (p < 0.001) in the vitamin D deficient group (n = 29) and 0.21 +/- 0.28% (p = 0.001) in the vitamin D insufficient group (n = 23). The change in weight post-treatment was only significant in the vitamin D deficient group at -0.80 +/- 1.11 kg (p = 0.001). Overall, there were negative correlations between the changes in HbA1c and weight with the change in vitamin D (p < 0.05). CONCLUSION: This study shows that vitamin D and calcium replacement therapy in South Asian patients with T2DM causes a significant decrease in both HbA1c and weight, which may be attributed to the increase in vitamin D levels post-treatment.

Ramadan Education and Awareness in Diabetes (READ) programme for Muslims with Type 2 diabetes who fast during Ramadan.

BACKGROUND AND AIMS: During Ramadan, Muslims fast from dawn to dusk for one lunar month. The majority of Muslim diabetic patients are unaware of complications such as hypoglycaemia during fasting. The safety of fasting has not been assessed in the UK Muslim population with diabetes. The aim of this study was to determine the impact of Ramadan-focused education on weight and hypoglycaemic episodes during Ramadan in a Type 2 diabetic Muslim population taking oral glucose-lowering agents. METHODS: We retrospectively analysed two groups. Group A attended a structured education programme about physical activity, meal planning, glucose monitoring, hypoglycaemia, dosage and timing of medications. Group B did not. Hypoglycaemia was defined as home blood glucose < 3.5 mmol/l. RESULTS: There was a mean weight loss of 0.7 kg after Ramadan in group A, compared with a 0.6-kg mean weight gain in group B (P < 0.001). The weight changes observed were independent of the class of glucose-lowering agents used. There was a significant decrease in the total number of hypoglycaemic events in group A, from nine to five, compared with an increase in group B from nine to 36 (P < 0.001). The majority were in patients treated with short-acting sulphonylureas (group A-100%, group B-94%). At 12 months after attending the programme, glycated haemoglobin (HbA(1c)) reduction were sustained in group A. CONCLUSIONS: Ramadan-focused education in diabetes can empower patients to change their lifestyle during Ramadan. It minimizes the risk of hypoglycaemic events and prevents weight gain during this festive period for Muslims, which potentially benefits metabolic control.

Comparison of Humalog Mix 50 with human insulin Mix 30 in type 2 diabetes patients during Ramadan.

AIMS: To compare hypoglycaemic events, glycated haemoglobin (HbA1c) and changes in body weight in Muslim patients with Type 2 diabetes receiving Humalog Mix 50 and human Mixtard 30 twice daily during Ramadan fasting. METHODS: Data were collected from Muslim patients with Type 2 diabetes attending primary care practices in North-West London, who were on Mixtard 30 insulin twice daily before Ramadan. Group 1 had their evening insulin changed to Humalog Mix 50 (n = 26) 2 weeks before Ramadan, i.e. taking Mixtard 30 at predawn meal and Humalog Mix 50 at the sunset meal during Ramadan. As the major proportion of the daily caloric intake was consumed at the sunset meal, the rationale of switching the evening dose from human Mixtard 30 to Humalog Mix 50 was to provide more rapid-acting insulin that has shorter time of onset and peak time for the large evening meal to improve the postprandial glucose control without increasing the risk of hypoglycaemia. Group 2 continued on Mixtard 30 twice daily (n = 26). All patients received structured education about how to identify and manage hypoglycaemia during Ramadan. RESULTS: Group 1 had a mean HbA1c reduction of 0.48% (p = 0.0001) before and after Ramadan, whereas group 2 had a mean HbA1c increase of 0.28% (p = 0.007). Group 1 was associated with a small reduction of 0.04 (p = 0.81) in the mean number of hypoglycaemic events during Ramadan compared with before Ramadan, whereas group 2 was associated with an increase of 0.15 (p = 0.43), although these differences between the groups were not statistically significant following adjustment for baseline factors [LSM difference between groups = 0.135, p = 0.36, 95% confidence limits (-0.16, 0.43)]. CONCLUSION: Changing to humalog Mix 50 during Ramadan resulted in improvement in glycaemic control without increasing the incidence of hypoglycaemia.

True duplicate bladder exstrophy: a rare lesion.

A two-day-old newborn male child with a rare variant of exstrophy bladder was managed in our institute. The child has true duplicate bladder exstrophy which is extremely rare and only 8 cases reported in the world literature so far. We describe another one and briefly review the literature.

Vildagliptin therapy and hypoglycaemia in Muslim type 2 diabetes patients during Ramadan.

AIMS: To compare hypoglycaemic events, glycated haemoglobin (HbA(1c)) and changes in bodyweight in metformin-treated Muslim patients with type 2 diabetes receiving adjunctive treatment with vildagliptin or gliclazide during Ramadan fasting. METHODS: Data were collected from Muslim patients with type 2 diabetes attending primary care practices in North West London, whose HbA(1c) was > 8.5% despite treatment with metformin 2 g daily before Ramadan and who received gliclazide 160 mg twice daily (n = 26) or vildagliptin 50 mg twice daily (n = 26) in addition to metformin. Hypoglycaemic events, HbA(1c) and weight were recorded 2 weeks before and 10 days after the Ramadan fast. All patients received education about how to identify and manage hypoglycaemia during Ramadan. RESULTS: During Ramadan, at least one hypoglycaemic event (defined as blood glucose < 3.5 mmol/l with or without symptoms) was recorded in two patients receiving vildagliptin (7.7%) and 16 patients receiving gliclazide [61.5%; difference between groups -53.8%, 95% confidence interval (CI) -74.9 to -26.3, p < 0.001]. Vildagliptin was associated with a reduction in the mean number of hypoglycaemic events during Ramadan compared with before Ramadan, whereas gliclazide was associated with an increase (least squares mean difference between groups -0.66, 95% CI -1.20 to -0.13, p = 0.0168). Both gliclazide and vildagliptin were associated with similar reductions in HbA(1c) and a small, but insignificant, increase in weight. CONCLUSIONS: Appropriate treatment adjustments can lead to improved diabetes management during Ramadan, with avoidance of significant weight gain and improved glucose control without hypoglycaemia. The addition of vildagliptin to metformin therapy during Ramadan in Muslim patients with type 2 diabetes was associated with a reduction in the incidence of hypoglycaemia.

The role of arterial stimulation and simultaneous venous sampling in addition to cross-sectional imaging for localisation of biochemically proven insulinoma.

Insulinomas, although rare, cause considerable morbidity but are frequently amenable to surgical cure. Laparoscopic surgery can now be considered if the tumour is localised pre-operatively, but the optimal imaging approach has not been determined. The objective of this study was to evaluate the ability of different imaging investigations, including CT, MRI, endoscopic ultrasound, octreotide scintigraphy and arterial stimulation with simultaneous venous sampling (ASVS), to localise insulinomas. All patients with biochemically proven insulinoma at our institution underwent ASVS along with other imaging investigations as part of their routine investigation. The results of these investigations were compared with histological findings. Twenty-eight patients with biochemically proven insulinoma confirmed by histology were identified. Ultimately ASVS localised a lesion in all patients. Seventeen patients (61%) had laparoscopic surgery. Tumor-detection rates for other imaging investigations included 43.5% of cases using CT, 71% using MRI, 86% using endoscopic ultrasound and 33% using octreotide scintigraphy. In four patients, the ASVS was the only test to correctly localise the lesion. ASVS should be considered routinely before surgery to ensure accurate localisation of insulinomas.

Mitigating effects of some antidotes on fluoride and arsenic induced free radical toxicity in mice ovary.

The effects of oral administration of sodium fluoride (NaF) and/or arsenic trioxide (As(2)O(3)) (5 mg and 0.5 mg/kg body weight, respectively) for 30 days were investigated on free radical induced toxicity in the mouse ovary. The reversibility of the induced effects after withdrawal of NaF+As(2)O(3) treatment and by administration of antioxidant vitamins (C, E) and calcium alone as well as in combination were also studied. The combined treatment of NaF and As(2)O(3) impaired significantly (p<0.001) the production of free radical scavengers such as glutathione and ascorbic acid as well as antioxidant enzymes, namely, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (Cat), thereby increasing ovarian lipid peroxides (LPO) which might have rendered the ovary susceptible to injury. The withdrawal of the combined (NaF and As(2)O(3) for 30 days) treatment caused partial recovery in the ovary, which was more pronounced (p<0.001) by treatment with vitamin C, calcium, or vitamin E alone and in combination. Hence the induced toxicity was transient and reversible.

Prevalence of organ-specific autoantibodies in childhood- and adult-onset type 1 diabetes.

There are no studies that compare the prevalence of organ-specific autoantibodies (OSAs) between adult (>or= 16 years) and childhood-onset type 1 diabetes (T1D). We evaluated the prevalence of the following OSAs: thyroid peroxidase, thyroid receptor, parietal cell, intrinsic factor, tissue transglutaminase, adrenal cortex, mitochondrial, smooth muscle, liver kidney microsomal, and ovarian autoantibodies. Three hundred twenty-seven (327) adults were screened for one or more of these OSAs. The prevalence of all the OSAs studied was similar in both groups. The most prevalent OSA observed was tissue transglutaminase (childhood-onset disease = 14.3%; adult-onset disease = 13.6%). This study did not demonstrate a distinct difference in the prevalence of OSAs between adult- and childhood-onset T1D patients.

Ectopia cordis associated with Cantrell's pentalogy.

Cantrell's pentalogy with ectopia cordis is an extremely rare and lethal congenital anomaly, with a reported incidence of 1:100,000 births in developed countries. We report a neonate who presented with ectopia cordis along with cleft lower sternum, upper abdominal wall defect, ectopic umbilicus, diaphragmatic defect, and interventricular septal defect. The neonate had respiratory distress with peripheral cyanosis and died because of acidosis and electrolyte imbalance before surgical intervention could be undertaken. We discuss the case and present a brief review of literature and of embryogenesis.

Association of immune mediators at diagnosis of Type 1 diabetes with later clinical remission.

AIMS: We tested the hypothesis that systemic concentrations of cytokines, chemokines or soluble cytokine receptors predict or accompany clinical remission in Type 1 diabetes (T1D). METHODS: In a prospective, multicentre study, 48 patients with newly diagnosed T1D and 55 age-matched healthy control subjects were investigated. Blood was drawn 3-7 days after the diagnosis and then 3-4 months later. Patients were grouped into partial remitters or non-remitters by the degree of clinical improvement defined by HbA(1c) (threshold 7.5%) and daily insulin dose (threshold 0.38 IU/kg/day). Systemic concentrations of 17 immune mediators were analysed in serum or plasma. In addition, autoantibodies against insulin (IAA), IA-2 (IA-2A) and GAD65 (GADA) were quantified. RESULTS: All 17 immune mediators showed remarkable intra-individual stability in their systemic concentrations over time. As a consequence, partial remission was not accompanied by changes in mediator levels except for a moderate decrease of interleukin (IL)-1ra concentrations (P = 0.02) and IL-10 concentrations (P = 0.01) in non-remitters. Baseline levels were associated with the later clinical course in that low levels of interferon gamma (P = 0.01), IL-10 (P = 0.03) and IL-1R1 (P = 0.009) concentrations were observed in partial remitters. CONCLUSIONS: We conclude that the systemic immunoregulatory state at diagnosis of T1D is predictive of clinical improvement during the remission phase. There was no general change in systemic immune reactivity in the months after diagnosis and initiation of insulin therapy.

Association of interferon-gamma and interleukin 10 genotypes and serum levels with partial clinical remission in type 1 diabetes.

We studied whether serum interferon (IFN)-gamma or interleukin (IL)-10 levels and their corresponding functional polymorphic genotypes are associated with partial remission of type 1 diabetes (T1D). A multi-centre study was undertaken in patients with newly diagnosed T1D and matched controls. T1D patients were followed for 3 months and characterized for remission status. Partial clinical remission was defined as a daily insulin dose

Increased urinary dopamine excretion in association with bilateral carotid body tumours-- clinical, biochemical and genetic findings.

This report describes a rare case of a patient with increased urinary dopamine excretion in association with bilateral carotid body tumours. Excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and 4-hydroxy-3-methoxymandelic acid (HMMA) were within the reference ranges, and an (123)I-meta-iodobenzylguanidine (MIBG) scan showed uptake in the neck masses, with no other abnormal uptake anywhere else in the body. The patient is being managed conservatively as the tumours are not amenable to resection on account of their size and vascularity. There are only four previous case reports of dopamine-secreting tumours of the carotid body described in the literature, all of whom were women. The tumours were unilateral in three cases and bilateral in the fourth case. Familial cases of carotid body tumours have a higher prevalence of bilateral tumours than non-familial cases. Recent reports in the literature have suggested that a significant number of patients with extra-adrenal catecholamine-secreting paragangliomas have a genetic mutation in one of the identified susceptibility genes for catecholamine-secreting tumours, despite having no other affected family members, and a mutation has been found in the succinate dehydrogenase gene for this patient.

Exploring the idiotypes of insulin antibodies as markers for remission in Type 1 diabetes.

AIMS: Complete or partial remission can occur in newly diagnosed Type 1 diabetes patients. We created idiotype-specific reagents to explore the idiotypes of insulin antibodies (IA) in a patient in remission, and to compare with a patient who was not. METHODS: Phage display was used to create a library of phagotopes specific to insulin binding in four sera. Sera from a Type 1 diabetes subject deemed to have undergone remission were taken at diagnosis and again during remission. Sera from a non-remitter were taken at diagnosis and after 3 months on insulin. Phagotopes from the four sera were randomly selected and tested for insulin specificity in a radiobinding assay by using sera from remitters and non-remitters. RESULTS: IA-binding phagotope selected from serum during remission displaced insulin binding in all nine IA(+) remitters and all 10 IA(+) non-remitters. IA-binding phagotope selected from the non-remission patient (3 months after insulin therapy) displaced insulin binding in 8/9 IA(+) remitters and 8/10 IA(+) non-remitters. The consensus peptide sequences adduced from the phages were identical for both these phagotopes. Phagotopes derived from insulin autoantibody-positive individuals at diagnosis were unable to displace insulin binding in the IA(+) sera 3 months later, whether in remission or not. CONCLUSIONS: We have established the principle of using phage display in the investigation of insulin antibodies during remission in Type 1 diabetes. The immunological characteristics of IA 3 months after the introduction of insulin treatment were different from those at diagnosis of Type 1 diabetes (IAA). Using phage display technology, it was not possible to distinguish insulin antibodies according to remission status.

Differential immune response to B:9-23 insulin 1 and insulin 2 peptides in animal models of type 1 diabetes.

Mice have two insulin genes that differ in the insulin sequence by two amino acids, including the B9 position. Given prior studies of the B:9-23 insulin peptide in NOD mice, a fundamental question is whether the immune response to the B:9-23 peptide of the two insulins is identical. We investigate responses to the immunization with B:9-23 insulin 1 and 2 peptides in NOD and RIP-B7.1 Balb/c mice. NOD and F1 (Balb/c x C57/Bl6) B7.1 transgenic mice were given either B:9-23 insulin 1, B:9-23 insulin 2 or tetanus toxoid (TT) control peptide. Insulin autoantibodies (IAA), and anti-B:9-23 antibodies (IgG1 and IgG2c) were measured. Subcutaneous injection of the insulin 2 but not the insulin 1 peptide significantly protected NOD mice from diabetes. Conceptually similar, insulin 1 peptide immunization accelerated diabetes in the B7.1 mice compared with insulin 2 peptide. Insulin 1 and 2 peptides induced similar levels of IAA in the NOD mice except at week 26, where insulin 2 induced higher levels of IAA. Anti-IgG1 B:9-23 peptide antibodies were higher in the insulin 2 immunized group of NOD mice, while IgG2c anti-B:9-23 peptide antibodies were higher in the insulin 1 group. Adoptive transfer of splenocytes from insulin 1 immunized mice to NOD.scid mice demonstrated accelerated diabetogenicity. The protection afforded by insulin 2 peptide but not insulin 1 peptide in the NOD mouse is reflected by its predominant Th2 humoral response. This may relate to the protection conferred by the insulin 1 knockout when bred onto NOD mice in contrast to acceleration of disease with an insulin 2 knockout.

Interferon alpha--a potential link in the pathogenesis of viral-induced type 1 diabetes and autoimmunity.

The incidence of type 1 diabetes has been rapidly rising. Environmental factors such as viruses have been implicated as a possible agent accounting for this rise. Enteroviruses have recently been the focus in many research studies as a potential agent in the pathogenesis of type 1 diabetes. The mechanism of viral infection leading to beta cell destruction not only involves multiple pathways but also the cytokine-interferon alpha (IFN-alpha). Our hypothesis is that activation of toll receptors by double-stranded RNA or poly-IC (viral mimic) through induction of IFN-alpha may activate or accelerate immune-mediated beta cell destruction. Numerous clinical case reports have implicated that IFN-alpha therapy is associated with autoimmune diseases and that elevated serum IFN-alpha levels have been associated with type 1 diabetes. In multiple animal models, given specific genetic susceptibility, poly-IC can induce insulitis or diabetes. Therapeutic agents targeting IFN-alpha may potentially be beneficial in the prevention of type 1 diabetes and autoimmunity.