Huperzine A ameliorates cognitive deficits and oxidative stress in the hippocampus of rats exposed to acute hypobaric hypoxia.

Acute exposure to high altitudes can cause neurological dysfunction due to decreased oxygen availability to the brain. In this study, the protective effects of Huperzine A on cognitive deficits along with oxidative and apoptotic damage, due to acute hypobaric hypoxia, were investigated in male Sprague-Dawley rats. Rats were exposed to simulated hypobaric hypoxia at 6,000 m in a specially fabricated animal decompression chamber while receiving daily Huperzine A orally at the dose of 0.05 or 0.1 mg/kg body weight. After exposure to hypobaric hypoxia for 5 days, rats were trained in a Morris Water Maze for 5 consecutive days. Subsequent trials revealed Huperzine A supplementation at a dose of 0.1 mg/kg body weight restored spatial memory significantly, as evident from decreased escape latency and path length to reach the hidden platform, and the increase in number of times of crossing the former platform location and time spent in the former platform quadrant. In addition, after exposure to hypobaric hypoxia, animals were sacrificed and biomarkers of oxidative damage, such as reactive oxygen species, lipid peroxidation, lactate dehydrogenase activity, reduced glutathione, oxidized glutathione and superoxide dismutase were studied in the hippocampus. Expression levels of pro-apoptotic proteins (Bax, caspase-3) and anti-apoptotic protein (Bcl-2) of hippocampal tissues were evaluated by Western blotting. There was a significant increase in oxidative stress along with increased expression of apoptotic proteins in hypoxia exposed rats, which was significantly improved by oral Huperzine A at 0.1 mg/kg body weight. These results suggest that supplementation with Huperzine A improves cognitive deficits, reduces oxidative stress and inhibits the apoptotic cascade induced by acute hypobaric hypoxia.

Migraine and Cochlear Symptoms.

Migraine is one of the most common and highest burdens of disease. As a primary cerebral dysfunction illness, migraine might exhibit other system-related symptoms, including vestibular and cochlear symptoms. With the publication of the diagnostic criteria of vestibular migraine, the link between migraine and vestibular symptoms became clear. However, the relationship between migraine and cochlear symptoms is far from straightforward. Therefore, we focus on the correlation between migraine and deafness, sudden sensorineural hearing loss, acute tinnitus, and chronic tinnitus to better understand the relationship between migraine and cochlear symptoms.

Rare primary lymphoepithelioma-like carcinoma of the renal pelvis.

Lymphoepithelioma-like carcinoma (LELC) is a rare, malignant epithelial tumour which can arise within the upper urinary tract. This letter adds to a previous systematic review and cumulative analysis of 28 published upper urinary tract-LELC cases which provided insight into this disease; however, the current evidence does not provide clinicians with clear guidelines due to its rarity. Therefore, the aim was to report a new case of renal pelvis LELC presented in our hospital. In this instance, we were able to report treatment experience and long-term follow-up results. This patient presented with hypertension and haemturia which initiated further investigation. While ultrasound identified an hypechoic mass, no malignant cells were detected using cytological testing. Abdominal magnetic resonance imaging identified a slightly enhanced mass in the left renal pelvis with no evidence of lymph node metastasis. Ureteroscopic tumor biopsy suggested the existence of urothelial carcinoma, hence, laparoscopic radical left nephroureterectomy with bladder cuff excision was performed. Through patient-practitioner consultations, we decided to adopt a "watch and wait" approach after radical nephroureterectomy rather than administering chemotherapy. Although, we would encourage clinicians to record and publish cases to garner insight into this type of malignant disease.

Immunologic role of nitric oxide in acute rejection of golden hamster to rat liver xenotransplantation.

AIM: To evaluate the immunologic role and expression significances of nitric oxide(NO), nitric oxide synthase(NOS),and its isoenzyme in acute rejection to liver xenografts from golden hamster in rat. METHODS: Liver transplantations were randomly divided into five groups(n=6-9):isografts (group I); xenografts (group II); xenografts plus cyclosporine treatment (group III), xenografts plus cyclophosphamide treatment combined with splenectomy (group IV), and xenografts using cyclophosphamide in combination with splenectomy (group IV) and xenografts using splenectomy in addition to cyclophosphamide and cyclosporine treatments(group V). The levels of ALT,TNF-alpha, and nitric oxide production(NOx) in serum of reciprents were examined,and expressions of type II(iNOS) and type III (cNOS) nitric oxide synthase(NOS)-inducible NOS(iNOS) and constitutive NOS(cNOS) were observed by NADPH diaphorase histochemical and immunohistochemical staining. RESULTS: The level of serum ALT,activity of serum TNF-alpha and systemic levels of NO metabolite in groups II and IV were higher than those of groups I and V(serum ALT,2416+/-475, 2540+/-82.5) nkat.L(-1) vs (556.8+/-43.5, 677.30+/-38.2 ) nkat.L(-1), P<0.01;(serum TNF-alpha, 353.5+/-16.1, 444.6+/-28.1) ng.L(-1), vs 38.5+/-5.2, 52.0+/-5.7) ng.L(-1), P<0.01; (serum NOx 514.6+/-18.1, 336.0+/-43.0)nmol.g(-1), vs 26.1+/-5.7, 27.7+/-6.0)nmol.g(-1), P<0.01. Cyclosporine in group III can repress the cellular immune response and the synthesis of nitric oxide and the expression of NO synthase,but not prolong the liver xenograft survival. The over-expression of NOS,iNOS and cNOS in liver xenograft rejection in groups II and IV were detected by NADPH diaphorase histochemical and immunohistochemical staining. CONCLUSION: The degrees of acute rejection can be effectively repressed in golden hamster to rat liver xenografts with splenectomy and cyclosporine. Nitric oxide metabolites,and nitric oxide synthase and its isoenzymes,above all inducible NOS (iNOS) can be used as potential diagnostic markers for acute rejection in liver transplantation. The cellular localization of nitric oxide varies according to the immunologic status of liver xenografts,thus thinking that hepatocyte derived nitric oxide may be protective in the hyporesponsive state,but hepatic injury is likely triggered by centrilobular iNOS expression in the superresponsive state.

Protective effect of nitric oxide on hepatopulmonary syndrome from ischemia-reperfusion injury.

AIM: To evaluate immunological protection of nitric oxide (NO) in hepatopulmonary syndrome and probable mechanisms of ischemia-reperfusion (IR) injury in rat liver transplantation. METHODS: Sixty-six healthy male Wistar rats were randomly divided into three groups (11 donor/recipient pairs). In group II, organ preservation solution was lactated Ringer's solution with heparin 10, 000/µL at 4 °C. In groups I and III, the preservation solution added, respectively, L-arginine or N(G)-L-arginine methyl ester (L-NAME) (1 mmol/L) based on group II, and recipients were injected with L-arginine or L-NAME (50 mg/kg) in the anhepatic phase. Grafted livers in each group were stored for 6 h and implanted into recipients. Five rats were used for observation of postoperative survival in each group. The other six rats in each group were used to obtain tissue samples, and executed at 3 h and 24 h after transplantation. The levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α and NO metabolites (NOx) were detected, and expression of NO synthase, TNF-α and intercellular adhesion molecule 1 (ICAM-1) was examined by triphosphopyridine nucleotide diaphorase histochemical and immunohistochemical staining. RESULTS: By supplementing L-arginine to strengthen the NO pathway, a high survival rate was achieved and hepatic function was improved. One-week survival rate of grafted liver recipients in group I was significantly increased (28.8 ± 36.6 d vs 4 ± 1.7 d, P < 0.01) as compared with groups II and III. Serum levels of ALT in group I were 2-7 times less than those in groups II and III (P < 0.01). The cyclic guanosine monophosphate (cGMP) levels in liver tissue and NOx in group I were 3-4 times higher than those of group II after 3 h and 24 h reperfusion, while in group III, they were significantly reduced as compared with those in group II (P < 0.01). The levels of TNF-α in group I were significantly lower than in group II after 3 h and 24 h reperfusion (P < 0.01), while being significantly higher in group III than group II (P < 0.01). Histopathology revealed more severe tissue damage in graft liver and lung tissues, and a more severe inflammatory response of the recipient after using NO synthase inhibitor, while the pathological damage to grafted liver and the recipient's lung tissues was significantly reduced in group I after 3 h and 24 h reperfusion. A small amount of constitutive NO synthase (cNOS) was expressed in liver endothelial cells after 6 h cold storage, but there was no expression of inducible NO synthase (iNOS). Expression of cNOS was particularly significant in vascular endothelial cells and liver cells at 3 h and 24 h after reperfusion in group II, but expression of iNOS and ICAM-1 was low in group I. There was diffuse strong expression of ICAM-1 and TNF-α in group III at 3 h after reperfusion. CONCLUSION: The NO/cGMP pathway may be critical in successful organ transplantation, especially in treating hepatopulmonary syndrome during cold IR injury in rat orthotopic liver transplantation.