Modeling type 2 diabetes in rats by administering tacrolimus.

The prevalence of diabetes is rapidly increasing. The current number of diagnosed cases is ~422 million, expected to reach ~640 million by 2040. Type 2 diabetes, which constitutes ~95% of the cases, is characterized by insulin resistance and a progressive loss of ß-cell function. Despite intense research efforts, no treatments are yet able to cure the disease or halt its progression. Since all existing animal models of type 2 diabetes have serious drawbacks, one is needed that represents the complete pathogenesis, is low cost and non-obese, and can be developed relatively quickly. The aim of this study was to evaluate a low-cost, non-obese model of type 2 diabetes engendered by administering a daily high dose of tacrolimus (an immunosuppressant) to Wistar rats for 4 weeks. The biochemical and antioxidant markers were measured at basal and after the 4-week tacrolimus treatment. At week 4, the values of these parameters closely resembled those observed in human type 2 diabetes, including fasting blood glucose at 141.5 mg/dL, blood glucose greater than 200 mg/dL at 120 min of the glucose tolerance test, blood glucose at varied levels in the insulin tolerance test, and elevated levels of cholesterol and triglyceride. The tacrolimus treatment produced hypoinsulinemia and sustained hyperglycemia, probably explained by the alteration found in pancreatic ß-cell function and morphology. This model should certainly be instrumental for evaluating possible type 2 diabetes treatments, and for designing new immunosuppressants that do not cause pancreatic damage, type 2 diabetes, or new-onset diabetes after transplantation (NODAT).

Diabetic neuropathy: Molecular approach a treatment opportunity.

Diabetic neuropathy (DN) encompasses a group of clinical or subclinical manifestations involving a dysfunction in the peripheral nervous system. The cause of the dysfunction is the development of microvascular complications related to diabetes, a disease that affects about 381 million people worldwide. Approximately 50% of patients currently diagnosed with diabetes are expected to manifest DN in the next 10 years. The diagnosis can be made clinically by establishing a good patient history and delving into the symptoms to rule out other etiologies. Treatment of DN focuses on glycemic control and the use of medications to reduce pain, including NSAIDs, antidepressants and antiepileptic drugs. The pathogenesis is of multifactorial origin, associated with various metabolic, vascular, inflammatory and neurodegenerative disorders. The three fundamental cellular alterations participating in the development of DN are chronic inflammation, endothelial dysfunction and oxidative stress. Since the combination of all three is capable of giving rise to nerve ischemia and direct axonal injury, these factors play a key role in the development of polyneuropathy. However, neuronal and microvascular changes do not occur in the same way in all patients with DN, some of whom have no detectable blood abnormalities.

Arsenic exposure: A public health problem leading to several cancers.

Arsenic, a metalloid and naturally occurring element, is one of the most abundant elements in the earth's crust. Water is contaminated by arsenic through natural sources (underground water, minerals and geothermal processes) and anthropogenic sources such as mining, industrial processes, and the production and use of pesticides. Humans are exposed to arsenic mainly by drinking contaminated water, and secondarily through inhalation and skin contact. Arsenic exposure is associated with the development of vascular disease, including stroke, ischemic heart disease and peripheral vascular disease. Also, arsenic increases the risk of tumors of bladder, lungs, kidneys and liver, according to the International Agency for Research on Cancer and the Food and Drug Administration. Once ingested, an estimated 70-90% of inorganic arsenic is absorbed by the gastrointestinal tract and widely distributed through the blood to different organs, primarily to the liver, kidneys, lungs and bladder and secondarily to muscle and nerve tissue. Arsenic accumulates in the organs, especially in the liver. Its excretion mostly takes place through urination. The toxicokinetics of arsenic depends on the duration of exposure, pathway of ingestion, physicochemical characteristics of the compound, and affected biological species. The present review outlines of arsenic toxic effects focusing on different cancer types whit highest prevalence's by exposure to this metalloid and signaling pathways of carcinogenesis.

Evaluation of risk factors in the development of type 2 diabetes in a Mexican population.

Type 2 diabetes (T2D), which causes many adverse effects such as endothelial dysfunction and cardiovascular disease, affects approximately 425 million people worldwide. However, about half have not yet been diagnosed. For what is recommended the use of screening tools to identify individuals at risk for T2D or in the early stages of the disease in order to impement preventive strategies or early treatment. According to a widely used survey, the FINDRISC scale, a hereditary family history of T2D (FH-T2D) is as important a risk factor as having had high glucose levels. The aim of the present study was to carry out non-probabilistic sampling in a Mexican population to evaluate key factors in the development of diabetes. The participants were divided into three groups: with and without FH-T2D and diagnosed with T2D. A comparison of the groups with and without FH-T2D revealed higher values in the former for body mass index (BMI: 24.5 vs 21.9 kg/m2), glycosylated hemoglobin [Hb1Ac: 5.775% (39 mmol/mol) vs 4.825% (29 mmol/mol)] and triglycerides (164.18 vs 68.12 mg/dL), and a lower value for the BH4/BH2 index (0.7846 vs 1.6117). These results indicate significant metabolic alterations and endothelial dysfunction for the FH-T2D group. This strongly suggests the need to screen individuals with a family history of inherited T2D based on their level of HbA1c, triglycerides and BH4.

A review of the impact of oxidative stress and some antioxidant therapies on renal damage.

An increase in the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to complications during chronic kidney disease (CKD). This increase essentially derives from the impairment of natural antioxidant systems of the organism. The resulting oxidative stress produces damage to kidney tissue, especially by affecting nephrons and more generally by disrupting the function and structure of the glomerulus and interstitial tubule. This leads to a rapid decline in the condition of the patient and finally renal failure. Possible causes of kidney tissue damage are explored, as are different therapies, especially those related to the administration of antioxidants.

'Inverse' temporomandibular joint dislocation.

Temporomandibular joint (TMJ) dislocation can be classified into four groups (anterior, posterior, lateral, and superior) depending on the direction of displacement and the location of the condylar head. All the groups are rare except for anterior dislocation. 'Inverse' TMJ dislocation is a bilateral anterior and superior dislocation with impaction of the mandible over the maxilla; to the authors' knowledge only two cases have previously been reported in the literature. Inverse TMJ dislocation has unique clinical and radiographic findings, which are described for this case.

Reproductive response in supplemented heifers in the humid tropics of Costa Rica.

To evaluate the effect of two supplementary diets to determine the consequence on productive and reproductive performance in heifers (Bos indicus x Bos taurus) averaging between 24 and 36 months of age and grazing tropical pastures, two trials were conducted. Thirty animals (initial BW 325.1+/-33.6 kg) were divided in two groups in the initial study: supplemented (SG) and control (CG); SG received a concentrate (5.5% CP and 2.85 Mcal/kg of DE dry matter basis) at 1% of body weight (BW). In the second study, 45 heifers (initial BW 332.6+/-29.3 kg) were assigned in two treatments, with the same amount of supplement (1% BW) but with a greater nutrient content (13% CP and 3.15 Mcal/kg of DE). The proportion of animals with a corpus luteum at the end of each study was greater in the supplemented groups (P<0.05). Ovarian follicular dynamics was similar between groups in the first study, but in the second study there were more heifers in the SG group with follicles larger than 9 mm in diameter (P<0.05). Pregnancy rate was similar for SG and CG (P>0.05). The response to a regimen of estrous synchronization in both trials was numerically superior in the SG group. No differences were observed in the length of estrus. Daily gain and body condition score were similar for supplemented and control groups (0.27 compared with -0.06 in the first study and 0.90 kg compared with 0.60 in the second study, respectively). Dietary supplementation improved the number of animals initiating estrous cycles and the expression of estrus when compared with unsupplemented control heifers. The dietary regimens imposed in these studies appear to be an adequate for the management of growing heifers destined to a reproductive program.

Identification of a protein kinase from Dictyostelium with homology to the novel catalytic domain of myosin heavy chain kinase A.

Myosin II assembly and localization into the cytoskeleton is regulated by heavy chain phosphorylation in Dictyostelium. The enzyme myosin heavy chain kinase A (MHCK A) has been shown previously to drive myosin filament disassembly in vitro and in vivo. MHCK A is noteworthy in that its catalytic domain is unrelated to the conventional families of eukaryotic protein kinases. We report here the cloning and initial biochemical characterization of another kinase from Dictyostelium that is related to MHCK A. When the segment of this protein that is similar to the MHCK A catalytic domain was expressed in bacteria, the resultant protein displayed efficient autophosphorylation, phosphorylated Dictyostelium myosin II, and also phosphorylated a peptide substrate corresponding to a portion of the myosin II tail. We have therefore named this gene myosin heavy chain kinase B. These results provide the first confirmation that sequences in other proteins that are related to the MHCK A catalytic domain can also encode protein kinase activity. It is likely that the related segments of homology present in rat eukaryotic elongation factor-2 kinase and a putative nematode eukaryotic elongation factor-2 kinase also encode the catalytic domains of those enzymes.

Desarrollo puberal en escolares de Merida. / Pubertal development in school children of Merida

Dentro del estudio tranversal de crecimiento y desarrollo de jovenes escolares meridenos, se evaluo el desarrollo puberal de los mismos. La poblacion estudiada comprendio 1.946 escolares; 1.044 hembras y 902 varones, cuyas edades oscilaban entre 7 y 20 anos. De estos, 342 varones, y 535 hembras presentaron algun grado de desarrollo puberal se utilizaron los estadios de 1 a 5 de Tanner, para glandula mamaria (GM), vello pubiano (VP) y genitales (G). El desarrolo testicular se evaluo utilizando el orquidometro de Prader, y la edad de la menarquia de acuerdo al metodo de "statu quo". Los resultados obtenidos en las hembras dieron una media (X +/- D.T.) 12,19 +/- 1,29 para GM2; 12,14 +/- 0,96 para VP2; 16,05 +/- 1,71 para GM5; 15,09 +/- 1,76 para VP2. La menarquia se presento a los 12,55 +/- 1,29. Para los varones, una media de 13,35 +/- 0,90 en G2 13,37 +/- 1,13 para VP2; 16,59 +/- 1,95 para G5 y 16,79 +/- 2,33 para VP5.En cuanto al volumen testicular el estadio adulto lo alcazaron en promedio a los 15,59 +/- 3,15 anos. Comparando las muestras de varones y hembras meridenos con los resultados previos de los autores en ninos de Caracas, conseguimos que los meridenos inician y finalizan mas tardiamente la pubertad. En relacion a datos publicados para Cuba, EE.UU e Inglaterra, nuestros ninos indican su pubertad mas tardiamente, pero alzanzan su madurez dentro de los limites establecidos en esas investigaciones