Lercanidipine decreases vascular matrix metalloproteinase-2 activity and protects against vascular dysfunction in diabetic rats

Abnormal matrix metalloproteinases (MMPs) activity causes cardiovascular diseases. Because hyperglycemia increase MMPs activities through increased oxidative stress. we hypothesized that antioxidant effects produced by lercanidipine could attenuate the increases in MMP-2 expression/activity in diabetic rats. Control and diabetic (alloxan-induced diabetes) rats received lercanidipine 2.5 mg/kg/day (or tap water) starting three weeks after alloxan (or vehicle) injections. Blood pressure was monitored weekly. After six weeks of treatment, vascular reactivity and structural changes were assessed in aortic rings. MMP-2 levels were determined by gelatin zymography, and MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined by fluorimetry. Lercanidipine produced antihypertensive effects (201 +/- 5 vs. 163 +/- 7 mm Hg in diabetic rats untreated and treated with lercaniclipine, respectively; P < 0.01) and reversed the impairment in endothelium-dependent vasorelaxation in diabetic rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of diabetic rats (both P < 0.001). Lercandipine attenuated the increases in oxidative stress and in MMP-2 (both P < 0.05). While diabetes induced no major structural changes, it caused a 16-fold increase in the ratio of MMP-2/TIMP-2 mRNA expression, which was completely reversed by lercanidipine (both P < 0.001). These results show that antioxidant and beneficial vascular effects produced by lercanidipine in diabetic rats are associated with reversion of the imbalance in vascular MMP-2MMP-2 expression. (C) 2008 Published by Elsevier B.V.

Jules Cotard (1840-1889) - His life and the unique syndrome which bears his name

Dr. Jules Cotard (1840-1889) was a Parisian neurologist who first described the delire des negations. Cotard's syndrome or Cotard's delusion comprises any one of a series of delusions ranging from the fixed and unshakable belief that one has lost organs, blood, or body parts to believing that one has lost one's soul or is dead. In its most profound form, the delusion takes the form of a professed belief that one does not exist. Encountered primarily in psychoses such as schizophrenia and bipolar disorder, Cotard's syndrome has also been described in organic lesions of the nondominant temporoparietal cortex as well as in migraine. Cotard's delusion is the only self-certifiable syndrome of delusional psychosis. Jules Cotard, a Parisian neurologist and psychiatrist and former military surgeon, was one of the first to induce cerebral atrophy by the experimental embolization of cerebral arteries in animals and a pioneer in studies of the clinicopathologic correlates of cerebral atrophy secondary to perinatal and postnatal pathologic changes. He was the first to record that unilateral cerebral atrophy in infancy does not necessarily lead to aphasia and was also the pioneer of studies of altered conscious states in diabetic hyperglycemia.

Presencia de nectomonadas metaciclicas de L. pifanoi en la hipofaringe de Lutzomyia youngi y la ingestion de azúcares

Se evidencia la presencia de promastigotos metacíclicos de Leishmania pifanoi en el conducto hipofaríngeo de Lutzomyia youngi infectados experimentalmente por ingurgitación sobre lesiones tarsales de hámsteres. La aparición de metacíclicos en la hipofaringe, cuya morfología se ilustra, ocurre entre los 5 y 9 días de desarrollo postprandial y es más frecuente en insectos alimentados con sacarosa comercial no refinada. Se investiga el papel de derivados aminados de glucosa y galactosa y también de aminoácidos, en la promoción y migración de los metacíclicos.

Blood glucose control in diabetes patients seen in primary health care centers

OBJECTIVE: To identify factors associated to poor glycemic control among diabetic patients seen at primary health care centers. METHODS: A cross-sectional study was carried out in a sample of 372 diabetic patients attending 32 primary health care centers in southern Brazil. Data on three hierarchical levels of health unit infrastructure, medical care and patient characteristics were collected. RESULTS: The frequency of poor glycemic control was 50.5%. Multivariate analysis (multilevel method) showed that patients with body mass indexes below 27 kg/m², patients on oral hypoglycemic agents or insulin, and patients diagnosed as diabetic over five years prior to the interview were more likely to present poor glycemic control when compared to their counterparts. CONCLUSIONS: Given the hierarchical data structuring, all associations found suggest that factors associated to hyperglycemia are related to patient-level characteristics.

Sensibilidade à insulina pós-prandial: mecanismos fisiológicos e de activação e fisiopatologia na obesidade

RESUMO A acção hipoglicemiante da insulina é máxima no estado pós-prandial e depende da substância hepática sensibilizadora da insulina (HISS). Esta dissertação visa o estudo do mecanismo de acção da insulina no estado pós-prandial e em particular da via dependente da HISS, em modelos animais fisiológicos e patológicos (obesidade e diabetes mellitus tipo 2). Avaliaram-se diferentes tipos de refeição quanto ao seu efeito potenciador da acção da insulina, em ratos Sprague-Dawley (modelo fisiológico). A administração intragástrica de glícidos não afecta a acção da insulina, mas a refeição mista (lípidos, glícidos e proteínas), promove a sensibilização para a acção da insulina, através de um processo que parece ser iniciado no intestino e envolve a activação da via da HISS. Nos estudos de obesidade, o primeiro modelo utilizado foi o rato alimentado com dieta hiperlipídica (HFD), no qual se observou uma insulinorresistência pós-prandial devida quase exclusivamente à perda de acção da HISS, que se correlaciona com a adiposidade (corporal e abdominal) e parece ser devida à diminuição da sua síntese. O segundo modelo de obesidade usado foi o rato Zucker obeso (OZR), modelo genético que apresenta uma diminuição idêntica de ambas as componentes de acção da insulina (dependente e independente da HISS). A alteração na via da HISS parece localizar-se a jusante da sua síntese, sugerindo que um ou vários pontos comuns entre as vias de sinalização intracelular da HISS e da insulina per se estão alterados, resultando num diminuto aporte de glucose. No OZR, a acção da HISS não se altera com a idade, apresentando-se baixa também às 52 semanas de idade. Em ratos não obesos (LZR), a acção da HISS diminui entre as 9 e 52 semanas, sendo acompanhada por um decréscimo menos acentuado, embora significativo, da acção da insulina per se. A diminuição da acção da HISS com a idade parece ser a principal causa de insulinorresistência pós-prandial em LZR velhos, não se agravando no OZR. No modelo de diabetes tipo 2 estudado, o rato Zucker diabético (ZDF), também ambas as componentes de acção da insulina estavam diminuídas. No entanto, a alimentação com ração Purina, ligeiramente mais energética e lipídica do que a ração standard, agrava a disfunção da via da HISS nestes animais, sugerindo que a sensibilidade à insulina em ratos ZDF é muito susceptível a factores nutricionais. A via da HISS é essencial para potenciar a acção da insulina do estado de jejum para o pós-prandial e a sua disfunção é em grande medida responsável pela insulinorresistência observada nos modelos animais de obesidade e diabetes estudados. xix SUMMARY Hypoglycemic insulin action is maximal in the postprandial state and depends on the hepatic insulin sensitizing substance (HISS). The present thesis focus on the postprandial insulin action and, in particular, on the HISS-dependent pathway, both in physiological and pathological (obesity and type 2 diabetes mellitus) animal models. Different meals were tested in Sprague-Dawley rats (physiological model) for their capacity to potentiate insulin action. It was observed that intragastric administration of either glucose or sucrose does not affect insulin sensitivity, unlike the mixed meal, composed of lipids carbohydrates and proteins, which significantly potentiated insulin action through a process that seems to be initiated at the intestine and involves activation of the HISS pathway. For the obesity studies, the first of the two obesity models used was the high fat-fed rat (HFD), in which the postprandial insulin resistance was almost exclusively caused by the decrease of HISS action, probably due to the impairment of HISS synthesis. This impairment correlates with both corporal and abdominal adiposity. The second obesity model used was the obese Zucker rat (OZR), a genetic model, which presented a similar impairment of both components of insulin action (HISSdependent and –independent). The modification in HISS pathway in OZR seems to be located downstream from HISS synthesis, that is, at its site of action – the skeletal muscle -, suggesting that one or several points common to both HISS and insulin per se signaling cascades are defective, resulting in a decreased glucose uptake. In OZR, HISS action does not decrease with age and is also low at 52 weeks of age. In non-obese rats (LZR), HISS action decreases from 9 to 52 weeks and it is accompanied by a lower, although significant, impairment of insulin action per se. HISS action impairment with aging seems to be the major cause of insulin resistance in old LZR, whereas insulin resistance is not aggravated in aging OZR. In the type 2 diabetes model, the diabetic Zucker rat (ZDF), both components of insulin action were also equally impaired. However, feeding the animals with Purina rat chow, which is slightly more caloric and more lipidic, induces additional HISS deterioration when compared with the standard lab diet, suggesting that insulin sensitivity in ZDF is very susceptible to nutritional factors. In conclusion, HISS pathway is essential to potentiate insulin action from the fasted to the fed state and its dysfunction is highly responsible for the insulin resistance observed in the obesity and diabetes animal models studied.

A comparative study of severe scorpion envenomation in children caused by Tityus bahiensis and Tityus serrulatus

From January 1984 to May 1994, 17 of 239 children under 15 years old stung by Tityus serrulatus (15.1%) or Tityus bahiensis (84.9%) presented severe envenoming. Of these 17 patients (1-11 years old; median=2 yr) 14 were stung by T.serrulatus and three by T.bahiensis. All of them received scorpion antivenom i.v. at times ranging from 45 min. to 5 h after the accident (median=2h). On admission, the main clinical manifestations and laboratory and electrocardiographic changes were: vomiting (17), diaphoresis (15), tachycardia (14), prostration (10), tachypnea (8), arterial hypertension (7), arterial hypotension (5), tremors (5), hypothermia (4), hyperglycemia (17), leukocytosis (16/16), hypokalemia (13/17), increased CK-MB enzyme activity (>6% of the total CK, 11/12), hyperamylasemia (11/14), sinusal tachycardia (16/17) and a myocardial infarction-like pattern (11/17). Six patients stung by T.serrulatus had depressed left ventricular systolic function assessed by means of echocardiography. Of these, five presented pulmonary edema and four had shock. A child aged two-years old presented severe respiratory failure and died 65 h after being stung by T.serrulatus. Severe envenomations caused by T.serrulatus were 26.2 times more frequent than those caused by T.bahiensis (p<0.001).

Regulação integrada do metabolismo da glucose no estado pós-prandial : fisiologia e reversão de processos patológicos

Resumo: Os mecanismos que regulam a homeostase da glucose no pós-prandial são distintos dos mecanismos desencadeados em situações de jejum. Desta forma o fígado parece desempenhar um papel fundamental na acção periférica da insulina após a refeição através de um mecanismo que envolve os nervos parassimpáticos hepáticos e o óxido nítrico (NO). Esta dissertação procura evidenciar a importância de ambos na fi siologia de manutenção da glicémia pós-prandial e na fi siopatologia da resistência à insulina. Dos resultados obtidos observou-se que após a administração de uma refeição mista o perfi l glicémico foi distinto em animais com ou sem ablação dos nervos parassimpáticos hepáticos. A desnervação parassimpática hepática aumentou as excursões de glucose imediatamente após a refeição. Estas diferenças nas excursões de glucose dependentes do parassimpático ocorreram devido a uma diminuição da clearance de glucose, sem que fosse afectada a taxa de aparecimento de glucose no sangue, a produção endógena de glucose e secreção de insulina ou péptido-C. Este aumento das excursões de glucose revelou-se ser devida à diminuição da clearance de glucose pós-prandial exclusivamente no músculo-esquelético, coração e o rim. Concluiu-se que o fígado teria uma função endócrina nestes três órgãos. Surgiu assim a hipótese dos S-nitrosotiois (RSNOs) poderem mimetizar essa resposta endócrina. Testou-se o seu efeito in vivo na sensibilidade à insulina. Para níveis baixos de sensibilidade à insulina, como jejum, desnervação no estado pós-prandial e resistência à insulina os RSNOs potenciaram a sensibilidade à insulina para valores semelhantes ao pós-prandial indicando-os como potenciais fármacos no tratamento da resistência à insulina. O NO e seus derivados ganharam assim uma evidência cada vez maior na acção periférica da insulina e portanto fez-se uma caracterização dos seus níveis desde a fi siologia à fi siopatologia. Os resultados obtidos nesta dissertação permitiram correlacionar a sintetase de óxido nítrico (NOS), enzima responsável pela síntese de NO como um possível marcador da resistência à insulina. Os resultados obtidos contribuíram substancialmente para compreender os mecanismos fi siológicos e fi siopatológicos de manutenção da glicémia após a refeição, colocando o fígado como órgão primordial na regulação periférica (extra-hepática) da captação de glucose.-------- ABSTRACT: The mechanisms responsible for the postprandial response are different from the ones in the fasted state. Therefore the liver seems to play a fundamental role in postprandial insulin action through a mechanism that evolves the hepatic parasympathetic nerves (HPN) and nitric oxide (NO). This work focused on the importance of both, HPN and NO, on postprandial glycemic control and on the pathophysiology of insulin resistance. We observed that after administration of a mixed meal the glycemic profi les with or without the parasympathetic nerves were distinct, increasing glucose excursions after ablation of HPN.This increase in glucose excursions was due to a decrease on the rate of glucose disappearance in extra-hepatic tissues. Glucose appearance rate, endogenous glucose production and insulin secretion were not related to this mechanism. The increase on glucose excursions after the ablation of hepatic parasympathetic system was due to a decrease on glucose clearance on extra-hepatic tissues, namely skeletal-muscle, heart and kidney. We concluded that the liver has an endocrine function on those tissues increasing their glucose uptake.This mechanism led to propose the hypothesis that S-nitrosothiols (RSNOs) could mimic this mechanism. Therefore RSNOs effects on insulin sensitivity were tested. For low insulin sensitivity levels, i.e. fasted state, ablation of the HPN or insulin resistance state induced by a high sucrose diet RSNOs increased insulin sensitivity to levels normally observed in the postprandial state. These results indicated these drugs as potential pharmacological tools in the treatment of insulin resistance. NO and their derivates emerged as fundamental parts of insulin action. A characterization of nitric oxide and nitric oxide synthase (NOS), the enzyme responsible for NO synthesis was part of the work performed. We concluded that NO could be used as a biomarker for insulin resistance states. This work contributed for understanding the mechanism underlying postprandial glycemic control indicating the liver as a key organ in the regulation of peripheral (extra-hepatic) insulin action.

PREVALENCE OF INTESTINAL PARASITISM AND ASSOCIATED SYMPTOMATOLOGY AMONG HEMODIALYSIS PATIENTS

Intestinal parasites are an important cause of morbidity and mortality. Immunocompromised individuals may develop more severe forms of these infections. Taking into account the immunity impairment in patients suffering from chronic renal failure (CRF), we will determine the prevalence and associated symptoms of intestinal parasites in these patients. Controls without CRF were used for comparison. Stool samples were collected and processed for microscopic identification of parasites using the Formalin-ether concentration method. For Cryptosporidium diagnosis, the ELISA technique was used. One hundred and ten fecal samples from hemodialysis patients were analyzed, as well as 86 from a community group used as control group. A result of 51.6% of intestinal parasites was observed in hemodialysis patients and 61.6% in the control group. Cryptosporidium and Blastocystis were the most common infections in patients with CRF (26.4% and 24.5%, respectively). Blastocystis was the most common infection in the control group (41.9%), however no individual was found positive for Cryptosporidium. Among the CRF patients, 73.6% were symptomatic, 54.3% of these tested positive for at least one parasite, in contrast to 44.8% in asymptomatic patients (p = 0.38). The most common symptoms in this group were flatulence (36.4%), asthenia (30.0%) and weight loss (30.0%). In the control group, 91.9% were symptomatic, 60.8% of these tested positive for at least one parasite, in contrast to 71.4% in asymptomatic patients (p = 0.703). A significant difference between the two groups was observed with regard to symptoms, with bloating, postprandial fullness, and abdominal pain being more frequent in the control group than in the hemodialysis group (all p < 0.05). Comparing symptomatic with asymptomatic, there was no association in either group between symptoms or the prevalence of parasitic infection, nor with the type of parasite or with multiple parasitic infections. Patients with chronic renal failure are frequent targets for renal transplantation, which as well as the inherent immunological impairment of the disease itself, results in immunosuppression by medication. For this reason, carriers of intestinal parasites with pathogenic potential can develop serious clinical complications influencing the success of transplantation. This fact, coupled with the high prevalence of intestinal parasites and the dissociation between symptoms and infection in CRF patients, suggests that the stool test should be incorporated in routine propedeutics. Furthermore, preventive measures for the acquisition of parasites through the fecal-oral contamination route should be introduced.

Diabetes Mellitus as a Risk Factor in Glaucoma's Physiopathology and Surgical Survival Time: A Literature Review

Glaucoma is a multifactorial condition under serious influence of many risk factors. The role of diabetes mellitus (DM) in glaucoma etiology or progression remains inconclusive. Although, the diabetic patients have different healing mechanism comparing to the general population and it has a possible-negative role on surgical outcomes. This review article attempts to analyze the association of both diseases, glaucoma and DM, before and after the surgery. The epidemiological studies, based mainly in population prevalence analyzes, have shown opposite outcomes in time and even in the most recent articles also the association remains inconclusive. On the contrary, the experimental models based on animal induced chronic hyperglycemia have shown an important association of both diseases, explained by common neurodegenerative mechanisms. Diabetic patients have a different wound healing process in the eye viz-a-viz other organs. The healing process is more and it results in lower surgical survival time, higher intraocular pressure (IOP) levels and, therefore, these patients usually need more medication to lower the IOP. Both randomized and nonrandomized retrospective and experimental molecular studies have shown the association between DM and glaucoma. Further studies are needed to get better explanations about outcomes on more recent surgical procedures and with the exponential use of antifibrotics. How to cite this article: Costa L, Cunha JP, Amado D, Pinto LA, Ferreira J. Diabetes Mellitus as a Risk Factor in Glaucoma's Physiopathology and Surgical Survival Time: A Literature Review.

Aspergillus niger causing tracheobronchitis and invasive pulmonary aspergillosis in a lung transplant recipient: case report

A case of invasive aspergillosis caused by Aspergillus niger in a lung transplant recipient is described. The patient presented hyperglycemia starting postoperatively, with other complications such as cytomegalovirus infection. The associated predisposing factors and other implications are discussed. Aspergillus niger seems to be a fungal species of low virulence that requires the presence of a severely immunosuppressed host to cause invasive disease.

The effects of a diet formulation with oats, soybeans, and flax on lipid profiles and uricemia in patients with AIDS and dyslipidemia

Introduction Although the initiation of highly active antiretroviral therapy (HAART) is accompanied by an attenuation of viral load, metabolic disorders characterized by hyperglycemia, dyslipidemia, and lipodystrophy are often observed in patients under this treatment. Certain foods, such as oat bran, soy protein, and flaxseed, have been shown to improve a patient's lipid profile despite possible increases in uricemia. Thus, a bioactive compound was formulated using these foods to help patients with HIV/AIDS control metabolic disorders resulting from HAART. Methods An uncontrolled before and after study was performed. The total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and uric acid before and after 3 months of consuming the formulation were compared in patients. The compound was formulated such that 40g (the recommended daily intake) contained approximately 10g of flaxseed, 20g of oat bran, and 10g of textured soy protein. Results The study population consisted of 139 patients, 31 of whom were included in the final analysis. There were no significant variations between the laboratory results obtained before and after consumption of the compound. Conclusions The regular consumption of the formulation together with individualized dietary guidance did not reduce lipid levels and did not contribute to an increase in uricemia in the study group. However, new studies with higher doses of the foods that compose the formulation should be encouraged to investigate whether these foods can positively influence the lipid profiles of these patients.

Low blood glucose levels and other complications during growth hormone supplementation in sepsis

Blood glucose levels in the high normal range or even moderate hyperglycemia is the expected profile in septic postoperative patients receiving high-calorie enteral alimentation. The addition of growth hormone as an anabolic agent should additionally reinforce this tendency. In a cancer patient undergoing partial gastrectomy with lymphadenectomy and suffering from postoperative subphrenic abscess and prolonged sepsis, tube feeding (38.3 kcal/kg/day) and growth hormone (0.17 IU/kg/day) were simultaneously administered for 25 days. Blood glucose levels were in the lower limits of the normal range before growth hormone introduction, and continued with a similar tendency during most of the therapeutic period. Two additional complications, namely heart arrest and peripheral edema, were documented during the same period. It is concluded that sepsis was the most likely mechanism for low glucose values, and that high-calorie enteral diet and growth hormone supplementation did not prevent that result. It is uncertain whether heart arrest was due to the drug, but its association with peripheral edema is well documented in clinical series.

Nutritional follow-up of critically ill infants receiving short term parenteral nutrition

Few studies have tried to characterize the efficacy of parenteral support of critically ill infants during short period of intensive care. We studied seventeen infants during five days of total parenteral hyperalimentation. Subsequently, according to the clinical conditions, the patients received nutritional support by parenteral, enteral route or both up to the 10th day. Evaluations were performed on the 1st, 5th, and 10th days. These included: clinical data (food intake and anthropometric measurements), haematological data (lymphocyte count), biochemical tests (albumin, transferrin, fibronectin, prealbumin, retinol-binding protein) and hormone assays (cortisol, insulin, glucagon). Anthropometric measurements revealed no significant difference between the first and second evaluations. Serum albumin and transferrin did not change significantly, but mean values of fibronectin (8.9 to 16 mg/dL), prealbumin (7.7 to 18 mg/dL), and retinol-binding protein (2.4 to 3.7 mg/dL) increased significantly (p < 0.05) from the 1st to the 10th day. The hormonal study showed no difference for insulin, glucagon, and cortisol when the three evaluations were compared. The mean value of the glucose/insulin ratio was of 25.7 in the 1st day and 15.5 in the 5th day, revealing a transitory supression of this hormone. Cortisol showed values above normal in the beginning of the study. We conclude that the anthropometric parameters were not useful due to the short time of the study; serum proteins, fibronectin, prealbumin, and retinol-binding protein were very sensitive indicators of nutritional status, and an elevated glucose/insulin ratio, associated with a slight tendency for increased cortisol levels suggest hypercatabolic state. The critically ill patient can benefit from an early metabolic support.

Morphologic and morphometric evaluation of pancreatic islets in chronic Chagas' disease

PURPOSE: Hyperglycemia and abnormal glucose tolerance tests observed in some patients with chronic Chagas' disease suggest the possibility of morphological changes in pancreatic islets and/or denervation. The purpose of this study was to describe the morphology and morphometry of pancreatic islets in chronic Chagas' disease. METHODS: Morphologic and computerized morphometric studies were performed in fragments of the head, body, and tail regions of the pancreas obtained at necropsies of 8 normal controls and 17 patients with chronic Chagas' disease: 8 with the digestive form (Megas) and 9 with the congestive heart failure form. RESULTS: The Megas group had a larger (p < 0.05) pancreatic islet area in the tail of the pancreas (10649.3 ± 4408.8 µm²) than the normal control (9481.8 ± 3242.4 µm²) and congestive heart failure (9475.1 ± 2104.9 µm²) groups; likewise, the density of the pancreatic islets (PI) was greater (1.2 ± 0.7 vs. 0.9 ± 0.6 vs. 1.9 ± 1.0 PI/mm², respectively). In the tail region of the pancreas of patients with the Megas form, there was a significant and positive correlation (r = +0.73) between the area and density of pancreatic islets. Discrete fibrosis and leukocytic infiltrates were found in pancreatic ganglia and pancreatic islets of the patients with Chagas' disease. Trypanosoma cruzi nests were not observed in the examined sections. Individuals with the Megas form of Chagas' disease showed increased area and density of pancreatic islets in the tail of the pancreas. CONCLUSION: The observed morphometric and morphologic alterations are consistent with functional changes in the pancreas, including glycemia and insulin disturbances.

Falciform ligament abscess: report of a case

Falciform ligament abscess is rare. We report a case of a 65-year-old man who presented with right upper quadrant abdominal pain, postprandial fullness, and fever. Computed tomography disclosed a cylindrical mass in the anterior abdomen that aroused suspicion of a hepatic abscess. At laparoscopic surgery, an abscess of the falciform ligament was found and drained. Two months later, the patient developed recurrence of the abscess secondary to acute calculous cholecystitis. Abscess drainage and cholecystectomy were performed. The presence of right uppper quadrant abdominal pain, epigastric tenderness, fever, leukocytosis, and a mass in the anterior abdomen should arouse suspicion of falciform ligament abscess. Its treatment consists of abscess drainage.