Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) / Drug-induced Hypersensitivity Syndrome (DIHS): a review of current concepts

The Drug Reaction with Eosinophilia and Systemic Symptoms syndrome, also known as Drug Induced Hypersensitivity Syndrome presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, causing damage to several systems, especially to the kidneys, heart, lungs, and pancreas. Recognition of this syndrome is of paramount importance, since the mortality rate is about 10% to 20%, and a specific therapy may be necessary. The pathogenesis is related to specific drugs, especially the aromatic anticonvulsants, altered immune response, sequential reactivation of herpes virus and association with HLA alleles. Early recognition of the syndrome and withdrawal of the offending drug are the most important and essential steps in the treatment of affected patients. Corticosteroids are the basis of the treatment of the syndrome, which may be associated with intravenous immunoglobulin and, in selected cases, Ganciclovir. The article reviews the current concepts involving this important manifestation of adverse drug reaction.

Unusual tomographic findings of complicated necrotizing pancreatitis

Acute pancreatitis (AP) is a potential life-threatening disease, which originates from inflammatory involvement of the pancreas and surrounding tissues. Serious complications eventuate and treatment is difficult. AP is classified in both interstitial edematous pancreatitis, which occurs in 70-80% of patients, and necrotizing pancreatitis, which occurs in 20-30% of patients. Diagnosis is based on the presence of two of the following criteria: abdominal pain, increased serum determination of amylase and/or lipase more than three times the reference value, and characteristic tomographic findings. Among the latter, there is the pancreatic and surrounding tissue damage as well as that related to distant organ involvement. This case report shows the fatal case of a male patient with a history of heavy alcoholic abuse admitted with the diagnosis of necrotizing pancreatitis. The authors call attention to the unusual tomographic findings; namely, a huge duodenal hematoma and a large hemoperitoneum, ischemic involvement of the spleen and kidneys, as well as pancreatic and peripancreatic necrosis.

Changes in renal glucose transporters in an animal model of metabolic syndrome

Considering the similarity between structural, hemodynamic, and functional changes of obesity-related renal disease and diabetic nephropathy, we hypothesized that renal glucose transporter changes occur in obesity as in diabetes. The aim of the work was to evaluate GLUT1 and GLUT2 in kidneys of an animal model of metabolic syndrome. Neonate spontaneously hypertensive rats (SHR), n=15/group, were treated with monosodium glutamate (5 mg/g) (MetS) for 9 days and compared with saline-treated Wistar-Kyoto (C) and SHR (H) rats. Lee index, systolic arterial pressure (SAP), glycemia, insulin resistance, triglycerides, and HDL cholesterol were evaluated at 3 and 6 months. Medullar GLUT1 and cortical GLUT2 were analyzed by Western blot. MetS vs. C and H rats had the highest Lee index (p<0.001) and insulin resistance (3-months C: 4.3±0.7, H: 3.9±0.9, MetS: 2.7±0.6; 6-months C: 4.2±0.6, H: 3.8±0.5, MetS: 2.4±0.6% • min−1, p<0.001), similar glycemia, and the lowest HDL-cholesterol at 6-months (p<0.001). In the MetS and H rats, SAP was higher vs. C at 3-months (p<0.001) and 6-months (C: 151±15, H: 190±11, MetS: 185±13 mm Hg, p<0.001) of age. GLUT1 was ̴ 13× lower (p<0.001) at 3-months, reestablishing its content at 6-months in MetS group, while GLUT2 was 2× higher (p<0.001) in this group at 6-months of age. Renal GLUT1 and GLUT2 are modulated in kidney of rats with metabolic syndrome, where obesity, insulin resistance and hypertension coexist, despite normoglycemia. Like in diabetes, cortical GLUT2 overexpression may contribute to the development of kidney disease

Renal GLUT1 reduction depends on angiotensin-converting enzyme inhibition in diabetic hypertensive rats

Aims: Angiotensin-converting enzyme (ACE) inhibitors are used in diabetic kidney disease to reduce systemic/intra-glomerular pressure. The objective of this study was to investigate whether reducing blood pressure (BP) could modulate renal glucose transporter expression, and urinary markers of diabetic nephropathy in diabetic hypertensive rats treated with ramipril or amlodipine. Main methods: Diabetes was induced in spontaneously-hypertensive rats (~210 g) by streptozotocin (50 mg/kg). Thirty days later, animals received ramipril 15 μg/kg/day (R, n =10), or amlodipine 10 mg/kg/day (A, n= 8,) or water (C, n = 10) by gavage. After 30-day treatment, body weight, glycaemia, urinary albumin and TGF-β1 (enzyme-linked immunosorbent assay) and BP (tail-cuff pressure method) were evaluated. Kidneys were removed for evaluation of renal cortex glucose transporters (Western blotting) and renal tissue ACE activity (fluorometric assay). Key findings: After treatments, body weight (p = 0.77) and glycaemia (p = 0.22) were similar among the groups. Systolic BP was similarly reduced (p < 0.001) in A and R vs. C (172.4 ± 3.2; 186.7 ± 3.7 and 202.2 ± 4.3 mm Hg; respectively). ACE activity (C: 0.903 ± 0.086; A: 0.654 ± 0.025, and R: 0.389 ± 0.057 mU/mg), albuminuria (C: 264.8 ± 15.4; A: 140.8 ± 13.5 and R: 102.8 ± 6.7 mg/24 h), and renal cortex GLUT1 content (C: 46.81 ± 4.54; A: 40.30 ± 5.39 and R: 26.89 ± 0.79 AU) decreased only in R (p < 0.001, p < 0.05 and p < 0.001; respectively). Significance:We concluded that the blockade of the renin–angiotensin systemwith ramipril reduced earlymarkers of diabetic nephropathy, a phenomenon that cannot be specifically related to decreased BP levels.

Morphometric analysis of fetal development of Cavia porcellus (Linnaeus, 1758) by ultrasonography: pilot study

Measurements on the growth process and placental development of the embryo and fetuses of Cavia porcellus were carried out using ultrasonography. Embryo, fetus, and placenta were monitored from Day 15 after mating day to the end of gestation. Based on linear and quadratic regressions, the following morphometric analysis showed a good indicator of the gestational age: placental diameter, biparietal diameter, renal length, and crown rump. The embryonic cardiac beat was first detected at an average of 22.5 days. The placental diameter showed constant increase from beginning of gestation then remained to term and presented a quadratic correlation with gestational age (r2 = 0.89). Mean placental diameter at the end of pregnancy was 3.5 ± 0.23 cm. By Day 30, it was possible to measure biparietal diameter, which followed a linear pattern of increase up to the end of gestation (r2 = 0.95). Mean biparietal diameter in the end of pregnancy was 1.94 ± 0.03 cm. Kidneys were firstly observed on Day 35 as hyperechoic structures without the distinction of medullar and cortical layers, thus the regression model equation between kidney length and gestational age presents a quadratic relationship (r2 = 0.7). The crown rump presented a simple linear growth, starting from 15 days of gestation, displaying a high correlation with the gestational age (r2 = 0.9). The offspring were born after an average gestation of 61.3 days. In this study, we conclude that biparietal diameter, placental diameter, and crown rump are adequate predictive parameters of gestational age in guinea pigs because they present high correlation index.