Protective role of melatonin and retinol palmitate in oxidative stress and hyperlipidemic nephropathy induced by adriamycin in rats

Abstract: We have studied the effects of melatonin and retinol palmitate (RP) on the nephropathy and oxidative stress induced by a single and high dose of adriamycin (AD) in Wistar male rats. A dose of melatonin (75 μg/ kg/day) and a dose of RP (0.25 g oily solution/kg/day, sc) were injected 3 and 9 days before and after the administration of AD (25 mg/kg, i.p.), respectively. After the decapitation, samples were taken from the neck vascular trunk in order to determine the triglycerides, total cholesterol, phospholipids, HDL-cholesterol, total proteins, urea, lipoperoxides, and reduced glutathione (GSH). We estimated the lipoperoxide and glutathione (GSH) contents in renal homogenates, and the excretion of proteins in urine over a 24 hr period. The administration of AD caused significant increases in proteinuria and in the other parameters studied [lipids (triglycerides, total cholesterol, phospholipids, and HDL-cholesterol), nonprotein nitrogen compounds, and lipoperoxides]. AD increased the lipoperoxide content, but it decreased the GSH content in the kidney. Both melatonin and RP, although melatonin more significantly, decreased the intensity of the changes produced by the administration of AD alone. In fact, melatonin was quite efficient in reducing the formation of lipoperoxides, restoring renal GSH content and decreasing remarkably the severity of proteinuria. These results support the powerful antioxidant action of melatonin at renal level and a lower antioxidant action of retinol. Likewise, these data reinforce the hypothesis which supports the pathogenetic role and the close relation between the oxidative stress and the expression of the nephropathy induced by AD. However, in spite of this obvious antioxidant effect of melatonin in the kidney, additional studies are required to establish accurately the role of this pineal indole in the regulation and dynamics of the antioxidative defense enzyme system, which neutralizes the damaging effect of free radicals, both endogenous and exogenous, in this organ.     

Identification of the receptor for erythropoietin by cross-linking to Friend virus-infected erythroid cells.

Erythropoietin (Epo) is a glycoprotein hormone that regulates erythroid development and interacts with surface receptors on developing erythroid cells. In this laboratory, a cell system with a relatively pure population of erythroid cells that respond to Epo has been developed. Immature erythroid cells are obtained from the spleens of mice infected with the anemia strain of Friend virus. The binding of 125I-labeled Epo (125I-Epo) to plasma membranes from these cells was studied in this investigation. 125I-Epo binding reached equilibrium within 20 min at 37 degrees C. Twenty percent of the receptors bound 125I-Epo with a Kd of 0.08 X 10(-9) M, while the remaining receptors bound the hormone with a Kd of 0.6 X 10(-9) M. In this study, a receptor for Epo was identified by cross-linking 125I-Epo to the receptor in intact cells and plasma membrane preparations using disuccinimidyl suberate. Polyacrylamide gel electrophoresis revealed two labeled bands of 100 and 85 kDa. The 85-kDa band was more heavily labeled (65%) than the 100-kDa band. Both bands were equally decreased when increasing amounts of unlabeled Epo were included in the binding mixture, indicating a specific interaction of 125I-Epo with the receptor.     

Symptomatic gastrointestinal amyloidosis in an HIV-infected patient

We report a rare case of symptomatic GI amyloidosis in an HIV-infected patient who ultimately developed uncontrollable upper GI bleeding. Gastric and jejunal biopsies revealed amyloidosis. Although the patient's history suggested the possibility of secondary amyloidosis, immunohistochemical staining together with serum electrophoresis and immunofixation revealed the presence of lambda light chains indicating primary amyloidosis.     

A bio-psycho-social approach to acute hypertensive disease in pregnancy

In this paper, the approach to the genesis of the acute hypertension of pregnancy, uses a conceptual and methodological perspective adjusted to its multifactorial nature; a set of questions with epidemiologic focus is proposed, in order to vinculate psychosocial factors with the biologic processes characteristic of this health problem.     

Necrotizing colitis in patients with cancer.

Necrotizing lesions of the colon occur in patients with malignancy. We identified 26 patients with cancer (23 with acute leukemia and three with solid tumors) who died from necrotizing colitis. Autopsies revealed three pathologic categories: pseudomembranous colitis in 69 per cent, agranulocytic colitis in 19 per cent and ischemic colitis in 12 per cent. Most died from sepsis. A comparison of characteristics was made with a control population matched for diagnosis, age, cause of death and duration of neoplasia. Nearly all patients in both groups had fever and were granulocytopenic secondary to chemotherapy. Most received antineoplastic and antimicrobial regimens during the month prior to their terminal illness. Abdominal pain and distention, stomatitis and necrotizing pharyngitis were frequently associated with colitis. Hyperbilirubinemia was a frequent late complication in those with colitis and the control group. Single and multiorganism septicemia were found more frequently in patients with colitis. As antemortem diagnosis was unusual, aggressive attempts at diagnosis are necessary to assess the true incidence of this disorder and the best therapy.     

Factors associated with microalbuminuria in type 1 diabetes mellitus: a cross-sectional study

In order to determine the prevalence of microalbuminuria in people with Type 1 diabetes mellitus (Type 1 DM) and identify factors associated with microalbuminuria, we studied 312 Type 1 DM patients attending in three hospitals in two Spanish regions over 6 months. Clinical characteristics, micro- and macro-vascular complications, blood pressure, 24-h urine albumin excretion, lipid profile, HbA1(c) levels, smoking habits, and family history of hypertension and diabetic nephropathy were recorded. Univariate analysis and multiple logistic regression were used to examine associations between these variables and the prevalence of microalbuminuria. We detected microalbuminuria in 29% of the patients. The prevalence of microalbuminuria was high during the second decade of diabetes and declined thereafter. Univariate analysis showed dyslipidaemia (P<0. 002), previously diagnosed hypertension (P<0.001), family history of hypertension (sibling alone P<0.006; mother alone P<0.05), family history of diabetic nephropathy (P<0.001), and laser-treated retinopathy (P<0.03) to be factors associated with the presence of microalbuminuria. Multiple logistic regression revealed an association between microalbuminuria and family history of nephropathy (OR 7.6, 3.6-16). In conclusion, in our sample the frequency of microalbuminuria seems to be related to the presence of dyslipidaemia, hypertension, and to a family history of hypertension or nephropathy.     

Studying host genetic background effects on multimorbidity of intestinal cancer development,type 2 diabetes and obesity in response to oral bacterial infection and high‐fat diet using the collaborative cross (CC) lines

BackgroundMultimorbidity of intestinal cancer (IC), type 2 diabetes (T2D) and obesity is a complex set of diseases, affected by environmental and genetic risk factors. High‐fat diet (HFD) and oral bacterial infection play important roles in the etiology of these diseases through inflammation and various biological mechanisms.MethodsTo study the complexity of this multimorbidity, we used the collaborative cross (CC) mouse genetics reference population. We aimed to study the multimorbidity of IC, T2D, and obesity using CC lines, measuring their responses to HFD and oral bacterial infection. The study used 63 mice of both sexes generated from two CC lines (IL557 and IL711). For 12 weeks, experimental mice were maintained on specific dietary regimes combined with co‐infection with oral bacteria Porphyromonas gingivalis and Fusobacterium nucleatum, while control groups were not infected. Body weight (BW) and results of a intraperitoneal glucose tolerance test (IPGTT) were recorded at the end of 12 weeks, after which length and size of the intestines were assessed for polyp counts.ResultsPolyp counts ranged between 2 and 10 per CC line. The combination of HFD and infection significantly reduced (P < .01) the colon polyp size of IL557 females to 2.5 cm², compared to the other groups. Comparing BW gain, IL557 males on HFD gained 18 g, while the females gained 10 g under the same conditions and showed the highest area under curve (AUC) values of 40 000‐45 000 (min mg/dL) in the IPGTT.ConclusionThe results show that mice from different genetic backgrounds respond differently to a high fat diet and oral infection in terms of polyp development and glucose tolerance, and this effect is gender related.     

Test of the auricular surface sex estimation method in fetuses and non-adults under 5 years old from the Lisbon and Granada Reference Collections

International Journal of Legal Medicine - Non-adult sex estimation is an active field of forensic inquiry as morphological variations between males and females are subtle, but observable, even from...