Gastroprotective effect of lupeol on ethanol-induced gastric damage and the underlying mechanism

The effect of lupeol, a natural pentacyclic triterpene on ethanol-induced gastric damage in mice was evaluated. The gastroprotection was assessed by determination of changes in mean gastric lesion area, quantification of mucosal non-protein sulfhydryls (NP-SH), and characterized using drugs that influence the endogenous prostaglandins, α₂-adrenoceptors, nitric oxide, K_ATP-channels, and intracellular calcium. Orally administered lupeol (3, 10, and 30 mg/kg) significantly and dose-dependently attenuated the ethanol-induced gastric damage by 39–69%, whereas the positive control N-acetylcysteine (NAC, 300 mg/kg, i.p.) afforded 32% protection. Both lupeol and NAC restored the NP-SH depleted by ethanol but the lupeol effect was only marginal. Lupeol gastroprotection was attenuated by indomethacin and L-NAME, the respective COX and NO-synthase inhibitors and was weakly sensitive to α₂-adrenergic antagonist yohimbine and K_ATP-channel blocker glibenclamide, but more profoundly to calcium blocker verapamil. These pharmacological effects of lupeol may synergistically contribute to alleviating the ethanol-associated gastric damage, which is multifactorial.     

Non-steroidal anti-inflammatory drugs-associated acute interstitial nephritis with granular tubular basement membrane deposits

Acute tubulo-interstitial nephritis (ATIN) is an important cause of acute renal failure resulting from a variety of insults, including immune complex-mediated tubulo-interstitial injury, but drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) are a far more frequent cause. Overall, as an entity, ATIN remains under-diagnosed, as symptoms resolve spontaneously if the medication is stopped. We report on a 14-year-old boy who developed acute renal failure 2 weeks after aortic valve surgery. He was put on aspirin following surgery and took ibuprofen for fever for nearly a week prior to presentation. He then presented to the emergency department feeling quite ill and was found to have a blood urea nitrogen (BUN) concentration of of 147 mg/dl, creatinine of 15.3 mg/dl and serum potassium of 8.7 mEq/l. Dialysis was immediately initiated. A kidney biopsy showed inflammatory infiltrate consistent with ATIN. However, in the tubular basement membrane (TBM), very intense granular deposits of polyclonal IgG and C3 were noted. He needed dialysis for 2 weeks and was treated successfully with steroids for 6 months. His renal recovery and disappearance of proteinuria took a year. In conclusion, this is a first report of NSAIDs-associated ATIN, showing deposits of granular immune complex present only in the TBM and not in the glomeruli.     

Thighplasty After Bariatric Surgery: Evaluation of Lymphatic Drainage in Lower Extremities

BACKGROUND: Bariatric surgery for morbid obesity achieves an accentuated weight loss, with skin and soft tissue redundancy in some corporal segments, including the thighs. The thigh lift is a plastic surgery that improves this redundant tissue in the medial thigh area, but this surgical procedure may have complications, such as inferior migration of the scar, delayed wound healing, vulvar distortion, and lymphatic system alterations. METHODS: To evaluate the effect of the thighplasty on the lymphatic system, 14 patients were prospectively included in this study. Lymphoscintigraphy was performed before thighplasty, and this result was compared to the new examination performed 6 months after thighplasty. The exclusion standards include patients with clinical alterations and abnormal lymphoscintigraphy in previous surgery. RESULTS: The statistical analysis was performed on 26 inferior members, according to exclusion standards. All the members had normal lymphoscintigraphy in the preoperative period. After thighplasty, eight members (30.8%) demonstrated abnormal lymphoscintigraphy (p = 0.008) resulting in significant functional and anatomic alterations in the lymphatic system. CONCLUSION: The thigh lift changes lymphatic drainage in lower extremities according to lymphoscintigraphy analyses.     

Signification biologique de 410 microcytoses de découverte fortuite chez des adultes jeunes

We have detected 410 microcytosis among biological tests of military people. These microcytosis are principally coumpounded by haemoglobin's abnormalities (minor thalassemia, sickle cell diseases, E haemoglobin cases and cases of C haemoglobin) and cases of iron deficiency, usually among women.     

Ectopic cutaneous schistosomiasis - Case report

Schistosomiasis mansoni is a systemic disease caused by a helminth of the schistosoma genus. The disease is generally asymptomatic or gastrointestinal symptoms may predominate. Skin lesions related to the disease are rarely diagnosed, even in endemic areas. The authors report the case of a young girl diagnosed with cutaneous schistosomiasis with involvement of the abdomen, back and scapular region. Schistosoma eggs were found in the lesions by histopathologic exam. There was no evidence of systemic involvement. Schistosomiasis must be included in the list of differential diagnosis of skin damage, especially in endemic areas, due to the potential consequences, in case of late diagnosis and treatment.     

NADPH-diaphorase Histochemical Labeling Patterns in the Hippocampal Neuropil and Visual Cortical Neurons in Weaned Rats Reared during Lactation on Different Litter Sizes

Abstract

Tissue distribution of nitric oxide-synthases was investigated in the rat hippocampus and visual cortex under nutritional changes induced by modification of the litter size. Young (30-45-days-old) rats, suckled in litters formed by 3, 6 or 12 pups (called small, medium and large litters, respectively), were studied by using nicotine-adenine-dinucleotide phosphate-diaphorase histochemistry (shortly, diaphorase), a simple and robust procedure to characterize tissue distribution of nitric oxide-synthases. We assessed morphometric features of the diaphorase-positive cells in visual cortex, and the neuropil histochemical activity in hippocampal CA1 and dentate gyrus using densitometry analysis. In the large-litter group, the labeled-cell density in white matter of area 17 was higher, as compared to the small-litter group. There was a clear trend, in the large-litter group, to lower values of soma area, dendritic field and branches per neuron, but the differences were not significant. Densitometry analysis of hippocampus revealed a significant increase in the relative neuropil histochemical activity of the dentate gyrus molecular layer in the larger litters, which may be associated to increased compensatory blood flow in the hippocampus. The pathophysiological mechanisms of the observed changes remain to be investigated.     

Serine proteases of Leishmania amazonensis as immunomodulatory and disease-aggravating components of the crude LaAg vaccine

We previously demonstrated that intradermal and intramuscular vaccination with Leishmania amazonensis promastigote antigens (LaAg) increases the susceptibility of BALB/c mice to cutaneous leishmaniasis. In this study, we investigated the role played by serine and cysteine proteases as disease-promoting components of LaAg. Mice were immunized by the intramuscular route with LaAg that was pre-treated with a pool of serine or cysteine protease inhibitors (SPi and CPi, respectively) prior to infection with L. amazonensis. Neutralization of either enzyme type reversed the disease-promoting effect of LaAg, as seen by the slower lesion development. However, the parasite burden was only effectively controlled in mice receiving SPi-treated LaAg. Protection was associated with diminished production of TGF-β and particularly IL-10 in response to parasite antigens by the lesion-draining lymph node cells of vaccinated mice relative to control. In vitro, soluble proteases isolated from LaAg (LaSP-Sol) directly activated IL-4, IL-10 and TGF-β production by immune cells. Like native LaAg, vaccination with LaSP-Sol primed mice to respond to parasite challenge with a strong Jones-Mote cutaneous hypersensitivity reaction, and increased susceptibility to infection. Furthermore, neutralization of serine but not cysteine proteases blocked the capacity of LaAg to sensitize mice for Jones-Mote reaction. Together, these results indicate that soluble serine proteases are key components of LaAg responsible for its disease-promoting immunity.     

Protection against cutaneous leishmaniasis by intranasal vaccination with lipophosphoglycan

We previously showed the opposing effect of systemic and mucosal vaccination with whole Leishmania amazonensis antigen (LaAg). Here, the role played by lipophosphoglycan (LPG) as the key disease-promoting component of intramuscular (i.m.) LaAg and its usefulness as a defined intranasal vaccine was investigated in murine cutaneous leishmaniasis. BALB/c mice were twice vaccinated by the i.m. route with 25mug of intact LaAg or with LaAg that was pretreated with anti-LPG 3A1-La monoclonal antibody, prior to infection with L. amazonensis. LPG neutralization rendered the otherwise disease-promoting LaAg antigen protective, as observed by the smaller lesion sizes and reduced parasite burden. The increased resistance was accompanied by a markedly lower antigen-driven TGF-beta and IL-10 responses in the lesion-draining lymph nodes, concomitant with significantly higher IFN-gamma production. To test for intranasal efficacy, 10 microg of affinity-purified LPG and its parental LaAg were twice instilled in the nostrils prior to L. amazonensis infection. In both cases, similarly slower lesion growth and lower parasite burden were found that was associated with increased IFN-gamma and IL-10 responses in the lesion-draining lymph nodes. These results support a role for LPG in the dual route-related effect of LaAg and shows its strong potential as a defined needle-free and adjuvant-free vaccine for cutaneous leishmaniasis.