PAX4 R192H is associated with younger onset of Type 2 diabetes in East Asians in Singapore

Aims

Young-onset T2D (YT2D) is associated with a more fulminant course and greater propensity for diabetic complications. The association of PAX4 R192H (rs2233580) variation with YT2D was inconsistent partly because of its Asian-specificity and under-representation of Asians in international consortiums. Interestingly, in our preliminary YT2D (mean?=?25?years old) cohort, the prevalence of PAX4 R192H variant was remarkably higher (21.4%) than the general population. Therefore, we sought to determine whether PAX4 R192H is associated with younger onset of T2D in our East Asian (Chinese) population.

A stimulatory effect of <Emphasis Type="Italic">Cassia occidentalis</Emphasis> on melanoblast differentiation and migration

In vitiligo, the active melanocytes in the epidermis are totally missing, whereas melanoblast cells in the outer root sheath of hair follicles are not affected. In an attempt to find potent repigmenting agents for vitiligo therapy, pod extracts of Cassia occidentalis was found to be effective in inducing differentiation and migration of mouse melanoblast cell line. Methanolic extract redissolved in DMSO at 12.5 μg/ml was found to cause 3.5- to 3.8-fold melanin induction in melb-a melanoblast cells after 4 days in treatment medium. In addition it induced the tyrosinase activity and altered melb-a cell morphology. Transwell migration assay showed the potential of this herbal candidate to induce direct migration of treated cells. To the best of our knowledge, this is the first report investigating the effect of Cassia occidentalis on the differentiation and migration of melanoblast cells. The findings of present study are significant in designing preclinical and clinical studies on the efficacy of C. occidentalis as a stimulant for skin repigmentation in vitiligo.     

Uterine Vascular Lesions

Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management.Key words: Uterine arteriovenous malformations, Uterine hemangioma, Placental chorioangioma, Uterine arteriovenous fistula, Uterine pseudoaneurysm, Acquired AVMVascular lesions of the uterus are very rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine vascular malformations can be congenital or acquired. Recently, there has been a rise in the number of reported cases following pregnancy, abortion, and curettage. Many of these studies report spontaneous resolution of vascular lesions during follow-up; in addition, there is an increasing trend toward use of uterine artery embolization (UAE) to treat these lesions. In many of the reported studies, the diagnosis of uterine vascular malformation was made as early as the second day after a delivery or an abortion. In a study by Timmerman and colleagues,¹ out of 30 cases reported as uterine AVM based on Doppler study, only 3 were true AVMs. Rufener and associates² conducted a sonologic evaluation of postpartum and postabortion uterine vascular lesions that were reported as AVMs; the study revealed that, on pathologic examination, none turned out to be AVMs. Thus, we observe that there is confusion with regard to the terminology of vascular lesions such as uterine AVM, vascular malformation, arteriovenous fistula (AVF), and non-AVM vascular abnormalities of the uterus. The term malformation, however, is generally used to describe defects in the structure of an organ or region of the body resulting from an intrinsically abnormal process of development. Therefore, spontaneous resolution of a malformation in a short period of time is unlikely. An investigation by Mulliken and Glowacki,³ published in 1982, provided the groundwork for a proper identification of vascular lesions. Vascular tumors grow by cellular (mainly endothelial) hyperplasia: the very common hemangioma is, in reality, a benign vascular tumor. In contrast, vascular malformations have a quiescent endothelium and are considered to be localized defects of vascular morphogenesis, likely caused by dysfunction in pathways regulating embryogenesis and vasculogenesis. Therefore, the terms vascular abnormality or vascular lesion seem to best describe hypervascular areas within the uterus seen on color Doppler ultrasound, unless they are proven to be an AVM by angiography or pathologic examination. Many of these vascular lesions are increasingly being managed by UAE. Although there have been various reports of successful pregnancy following UAE, there have also been reports of ectopic pregnancy following UAE.⁴It is important to correctly identify various vascular lesions in the uterus to avoid unnecessary invasive intervention. This article aims to familiarize the reader with various vascular lesions of the uterus and their management.Uterine AVM is a rare condition, and the true incidence is not yet known. A study by O’Brien and associates⁵ showed an incidence of AVM of 4.5% in 464 pelvic sonographic examinations performed for pelvic bleeding. AVM has been described in patients between 18 and 72 years of age, and may be congenital or acquired pathologic conditions.⁶ The congenital form is very rare and is the result of a defect in embryonic vascular differentiation or a premature arrest in the development of the capillary plexus leading to multiple abnormal connections between arteries and veins.⁷ These congenital AVMs often penetrate the surrounding tissue and can cause an elaborate collateral vascular network. Furthermore, these congenital lesions can grow as pregnancy progresses.⁸The International Society for the Study of Vascular Anomalies classification system divides vascular anomalies into two primary biologic categories: (1) vasoproliferative or vascular neoplasms and (2) vascular malformations. The major distinction between the two categories is whether there is increased endothelial cell turnover, which is ultimately determined by the identification of mitoses seen on histopathology. Vasoproliferative neoplasms have increased endothelial cell turnover (ie, they proliferate and undergo mitosis) because they are neoplasms. Vascular malformations do not have increased endothelial cell turnover; rather, they are structural abnormalities of the capillary, venous, lymphatic, and arterial system, and can be congenital or acquired.     

Cortisol promotes and integrates the osmotic competence of the organs in North African catfish (Clarias gariepinus Burchell): Evidence from in vivo and in situ approaches

The short-term in situ and long-term in vivo effects of cortisol were examined in North African catfish (Clarias gariepinus) to identify how this major corticosteroid integrates the osmotic competence of fish organs. In the in situ approach, the hydromineral effects of cortisol perfusion (75-300 ng ml⁻¹) for 20 min were tested and the indices of hydromineral and metabolic regulations were measured in our in vivo experimental fish after three alternate intraperitoneal cortisol injections (40 and 200 ng g⁻¹ body mass) for 5 days. Na⁺, K⁺-ATPase activity, a measure of cellular osmotic competence, responded to in situ and in vivo cortisol treatments. In situ cortisol delivery increased the Na⁺, K⁺-ATPase activity in the gill (P < 0.001) and kidney (P < 0.001) but decreased (P < 0.01) in the liver and showed no effect on intestine. In vivo cortisol treatment, on the contrary, increased Na⁺, K⁺-ATPase activity in the gills (P < 0.01), intestine (P < 0.05) and liver (P < 0.01) but decreased (P < 0.05) in the kidney. As expected, plasma cortisol increased (P < 0.001) with increasing doses of cortisol injections which produced direct effects on the metabolites and the mineral contents including the elevations of glucose (P < 0.05), lactate (P < 0.05) and Mg²⁺ (P < 0.05) and reductions of urea (P < 0.05), Na⁺ (P < 0.05) and K⁺ (P < 0.05) in the plasma. A decline of triiodothyronine (P < 0.01) occurred in the catfish after in vivo cortisol treatment and that implies a direct cortisol action on the homeostatic integration in this fish. Evidence is thus presented that in catfish cortisol regulates the whole body hydromineral and metabolite homeostasis by promoting and integrating the osmotic and metabolic functions of the multiple organ systems including liver.     

Antimutagenic and anti-oxidant activities of the non-steroidal anti-inflammatory drug celecoxib

1. Tumors arise and progress through the accumulation of serial genetic changes, including successive mutations, which involve activation of proto-oncogenes and inactivation of tumour suppressor genes, leading to the uncontrolled proliferation of progeny cells. The human body is continuously and unavoidably exposed to structurally diverse chemicals with established carcinogenic activity in animal models and/or mutagenic activity in short-term tests. 2. Celecoxib, a non-steroidal anti-inflammatory drug that specifically inhibits the enzyme cyclo-oxygenase-2, has been reported to be effective against certain types of cancers. The in vitro anti-oxidant and antimutagenic activities of the celecoxib were investigated in the present study using standard procedures. 3. The antimutagenic activity of celecoxib was determined using histidine mutant Salmonella typhimurium strains TA98, TA100, TA102 and TA1535 against directly acting mutagens (sodium azide (NaN3), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 4-nitro-o-phenylenediamine (NPDA) and doxorubicin) and mutagens needing activation (2-acetamidofluorene (2-AF) and 7,12-dimethylbenz [a] anthracene (DMBA)). 4. Celecoxib inhibited NaN3-, MNNG- and NPDA-induced mutations of TA100. The antimutagenicity of celecoxib (0.2 mg/plate) against the NaN3-induced mutation of TA1535 was 39.8% (P < 0.001). The MNNG-induced mutation of TA1535 was also inhibited by 0.3 mg/plate celecoxib (46.0%; P < 0.05). At concentrations of 0.2 mg/plate, celecoxib significantly inhibited NPDA- and doxorubicin-induced mutations of TA98 by 52.5 and 58.0%, respectively (P < 0.001 and P < 0.05, respectively). 5. The antimutagenic activity of 0.3 mg/plate celecoxib against 2-AF- and DMBA-induced mutations of TA98 was 81.76 and 98.1%, respectively (P < 0.001). 6. The anti-oxidant activity of celecoxib was determined by the inhibition of lipid peroxidation and superoxide and hydroxyl radical-scavenging activities. 7. The IC50 values of celecoxib for hydroxyl radical-scavenging and the inhibition of lipid peroxidation were 1.97 +/- 0.06 and 1.99 +/- 0.05 micromol/mL, respectively. Celecoxib had no superoxide radical scavenging-activity up to a concentration of 2.6 micromol/mL. 8. The in vitro antimutagenic and anti-oxidant activities of celecoxib indicate its possible therapeutic use as a cancer chemopreventive agent.     

Effect of stress on growth, pigment production and morphology of Monascus sp. in solid cultures

The aim of the current work was to study the influence of stress on pigment production in Monascus purpureus under solid-state fermentation. Thermal stress was induced by incubating the culture at various high temperatures. For giving osmotic stress, different concentration of NaCl and glycerol were added to the solid substrate prior to autoclaving. Morphological studies were done by light microscopy and scanning electron microscopy. When the cells were exposed to high temperature, high glycerol and salt concentration, significant changes in pigment production and growth were observed. High temperature (>45 degrees C) induced the production of more yellow pigments. High concentration of NaCl induced conidiation and caused a decrease in fungal biomass (up to 50%) but red pigment production increased from 11.86 OD/gds to 20.14 OD/gds. When subjected to glycerol stress, a significant increase in aerial mycelia was observed when compared with the control conditions. The results attain significance for exploiting the fungal culture of Monascus purpureus LPB 97 for producing colors of choice--red, or yellow, or increasing the yield of red pigments considerably. Thus, these results could well impact the commercial aspect of Monascus pigments for industrial application.     

Effect of extended colostrum feeding on the plasma profile of insulin, thyroid hormones and blood glucose of crossbred pre-ruminant calves

In the present study, the effect of extended colostrum feeding on certain physiological and endocrinological parameters of pre-ruminant crossbred calves from birth to one month of age was investigated. Estimation of blood glucose level, plasma concentration of anabolic hormones as thyroid hormones and insulin were performed and compared with control calves (G-I) which were fed with colostrum for the first three days of age and thereafter with the whole milk, till 30 days of age. There was steady increase in the blood glucose level (BGL) from birth to one month of age in both groups of calves, with the rise being slightly higher in the calves of G-II group, which is attributed to the action of glucagon by gluconeogenesis especially in the neonates. Intake and absorption of increased amounts of dietary proteins and amino acids in colostrum stimulated a significant increase in the plasma insulin concentration in G-II calves compared to G-I calves, over and above the accelerated tissue development of pancreas. Fluctuating levels of thyroid hormones in plasma of calves of both the groups suggested that the concentration of thyroid hormones were not influenced either by extended colostrum or whole milk feeding in calves, but rather followed a diurnal rhythm.