Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment

Cholestasis, or impaired bile flow, occurs in a wide variety of liver diseases and causes hepatic damage by retention and accumulation of toxic hydrophobic bile salts inducing persistent inflammation and oxidative stress. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and anti-inflammatory agent against autoimmune disease, on hepatic damage produced by double ligature of the extrahepatic biliary duct in Wistar Albino rats. Cholestasis was done by double ligature and section of the extrahepatic biliary duct (BDL). Leflunomide was given i.g. 10 mg/kg/day. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and levels of direct bilirubin. Malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO), catalase (CAT) and superoxide dismutase (SOD) were determined to the oxidative status in the liver tissue. Myeloperoxidase (MPO) activity and levels of tissue hydroxyproline (HPR) were determined to neutrophil activation and collagen accumulation, respectively. Further, histological changes were studied. Treatment with leflunomide markedly reduced serum transaminase activities as compared to BDL rats. At the same time leflunomide significantly inhibited increases in liver MDA, PC and NO levels and also attenuated the depletion of CAT and SOD in the liver after bile duct ligation. Similarly, increase in tissue MPO activity and HPR due to BDL was also attenuated by leflunomide treatment. These findings were supported by histopathological findings. These findings suggested that leflunomide can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress and inflammatory process.     

Sildenafil-related cerebral venous sinus thrombosis and papilledema: a case report of a rare entity

Neurological Sciences - We present a rare case of cerebral venous sinus thrombosis associated with long-term and high-dose use of sildenafil. A 29-year-old man was referred to our...     

Association between ACE and AGT polymorphism and cardiovascular risk in acromegalic patients

Purpose

Whether the renin–angiotensin–aldosterone system plays a role or not in the development of cardiovascular morbidity in acromegaly patients is unknown. The aim of the study was to investigate the association between ACE (I/D) and AGT (M235T) gene polymorphisms and cardiovascular and metabolic disorders in the acromegaly.

Methods

The study included one hundred and seventeen acromegalic patients (62 F/55 M, age: 50.2?±?12.3 years) and 106 healthy controls (92 F/14 M, age: 41.4?±?11.3 years). PCR method was used to evaluate the prevalence of ACE and AGT genotype.

Results

The genotypes of ACE polymorphism in acromegalic patients were distributed as follows; 41.0% (n: 48) for DD, 44.4% (n: 52) for ID and 14.5% (n: 17) for II genotype. The control group had significantly different distribution of the ACE polymorphism [48.1% (n: 51) for DD, 25.5% (n: 27) for ID and 26.4% (n: 28) for II genotype]compared to acromegalic group. Regarding AGT polymorphism, AGT-MT genotype was seen in 88.9% of the acromegalic patients while MM and TT genotype (9.4% and 1.7%, respectively) were present in the rest. The controls had similar distribution of the AGT genotype with the acromegaly group (80.2% MT genotype, 15.1% MM genotype and 4.7% TT genotype). Due to the small number of patients with TT allele (n: 2), T carriers for AGT genotype (AGT-MT+TT) were subgrouped and compared to those with AGT-MM group. ACE-DD, ID and II groups had similar anthropometric measures, blood pressure values and baseline GH and IGF-1 levels. Significantly higher baseline GH levels were found in AGT-MM group compared to T allele carriers [40 (16–60) vs. 12 (5–36) µg/L, p?<?0.05]. The compared groups in both polymorphisms had similar fasting plasma glucose levels. Patients with ACE-II genotype had significantly higher HDL-C levels compared to those with ACE-DD and ACE-ID polymorphisms (p?<?0.05) whereas there was no significant difference in lipid profile between AGT-MM group and AGT-T allele carriers. Moreover, the compared groups in both polymorphisms had similar distribution of hyperlipidemia, hypertension, impaired glucose metabolism (prediabetes or type 2 diabetes mellitus) and coronary artery disease. In terms of echocardiographic parameters, systolic and diastolic function was similar among the groups in ACE and AGT genotypes. Interestingly, AGT-MM group had higher mitral inflow A_peak values than T allele carriers (0.94?±?0.46 vs. 0.73?±?0.20; p?=?0.051). No significant difference was observed in LV mass index values in acromegalic patients among the groups in both polymorphisms.

Conclusions

Both ACE (I/D) and AGT (M235T) gene polymorphisms do not seem to have a significant effect on the development of clinical properties or cardiovascular comordities of acromegalic patients.

     

Correlations between cardiac troponin I, cardiac troponin T, and creatine phosphokinase MB elevation following successful percutaneous coronary intervention and prognostic value of each marker

AIMS: The aim of this prospective cohort study was to examine correlation between the postprocedural absolute rise of cardiac troponin (cTn-I), cardiac troponin T (cTn-T), and creatine phosphokinase MB (CK-MB), and predictive value of each marker for the long-term cardiac events following successful percutaneous coronary interventions. METHODS: The study consisted of 111 consecutive patients who had angiographically successful coronary balloon angioplasty with or without stent implantation. cTn-I, cTn-T, and CK-MB were measured before, immediately after the procedure, and every 6 hours for the first 24 hours. Patients were followed-up for major adverse cardiac events including acute myocardial infarction, death, recurrent angina, and revascularization for a period of 21+/-8.2 months. RESULTS: Total 45 patients (40%) had postprocedural cTn-I elevation, 27 patients (24%) cTn-T elevation, and 17 patients (15%) CK-MB elevation. There were strong correlations between the absolute values of the postprocedural maximal cTn-I and cTn-T, cTn-I and CK-MB, cTn-T and CK-MB (r: 0.64, r: 0.64, and r: 0.70 respectively, p<0.0001 for all correlations). There was also a significant concordance between the post-procedural positivity (higher than upper limit of normal) of cTn-I and cTn-T (kappa: 0.59), but CK-MB did not show significant concordances with c-Tn-T (kappa: 0.42), and cTn-I (kappa: 0.38). Long-term major cardiac events were observed in 29 patients (27%). Higher than 4-fold increase in cTn-I (log rank: 5.0, p: 0.02), and cTn-T (log rank: 10.7, p<0.001), and 2- to 4-fold in CK-MB (log rank: 17.9, p<0.0001) showed marked decremental effects on the event free survival. CONCLUSION: Although the cTn-I is found to be relatively more sensitive cardiac marker, cTn-T can be used as an alternative assay with significant correlation, concordance, and prospective value. Both troponins have predictive value for long-term event free survival; particularly 4-fold increase is associated with worse event free survival.     

Effect of parasitosis on allergic sensitization in rats sensitized with ovalbumin: Interaction between parasitosis and allergic sensitization

Some helminthic infections, especially nematode infections, may behave as allergens and induce allergic sensitization. In this study, the investigators explored whether infections withSyphacia muris andAspiculuris tetraptera have any effect on the development of allergen-induced cytokine responses and serum total immunoglobulin E (IgE) levels in ovalbumin (OVA)-sensitized rats. Four groups of male Wistar rats were studied. OVA sensitization was generated in 2 groups of rats; the rats in 1 group were infected and those in the other group were not. On day 21 after sensitization, tumor necrosis factor-α, interleukin-10, and total IgE levels in serum samples of rats were measured by enzyme-linked immunosorbent assay. The results showed that average concentrations of tumor necrosis factor-α and interleukin-10 were significantly greater in the group of rats infected with parasites and sensitized to OVA compared with the group uninfected with parasites and sensitized to OVA (P=.043 and P=.046, respectively). Upon comparison of total IgE concentrations, the group of rats infected with parasites and given saline solution showed higher levels compared with the group uninfected with parasites and given saline (P=.004). In conclusion, the investigators were unable to show a protective effect of an existing parasitic infection against the development of allergic sensitization upon exposure to OVA.     

Anorexia nervosa and Raynaud's phenomenon: a case report

OBJECTIVE: To describe and discuss potential relationships between anorexia nervosa (AN) and Raynaud's phenomenon, the course and concurrent treatment of these two disorders as they appeared simultaneously, and a potential treatment modification entailed in such concurrent therapies. BACKGROUND: Although Raynaud's phenomenon has been described during the course of AN, the associations and interactions between these two conditions are not clear. METHOD: We report the medical workup, treatment, and outcomes in a 19-year old female patient who developed Raynaud's phenomenon following the onset of AN. RESULTS: After treatment with nutritional rehabilitation, counseling, and individual and group therapy, the patient's weight, eating disorder-related behaviors, and attitudes improved significantly. Raynaud's related symptoms improved, following treatment with a calcium channel blocker and antiaggregant therapy. In conjunction with nutritional efforts to treat the patient's long-standing amenorrhea and osteopenia, the treatment team elected to also administer estrogen hormone in addition to oral calcium and vitamin D supplementation. Since oral contraceptives are to be avoided in patients with Raynaud's phenomenon who show clinical findings suggesting connective tissue disorder, the treatment team elected to treat this patient with transdermal hormone replacement therapy. CONCLUSION: The co-occurrence of AN and Raynaud's phenomenon merits close and persistent follow-up by a multidisciplinary team and may lead to alterations of usual therapeutic approaches.     

A Unique Case of Bilateral Synchronous Testicular Tumor with Concomitant Bilateral Diffuse Intratubular Germ Cell Neoplasia: Testis Sparing Surgery and Local Radiotherapy

Synchronous bilateral testicular germ cell tumors (TGCTs) are seen in exteremely rare cases. Although there is still no standard therapy for bilateral TGCTs, bilateral orchiectomy is recommended as the gold standard treatment. Nevertheless, it has some long-term problems, such as infertility and psychosocial difficulties, and thus some clinicians prefer to perform testis-sparing surgery in appropriate cases. We reviewed the first case of bilateral synchronous TGCT with concomittant bilateral diffuse intratubular germ cell neoplasia in a young single patient, who was treated by a left radical orchiectomy and right testis sparing-surgery with following local radiotherapy to the right residual testicular tissue with previous semen cryopreservation to maintain the ability to father children. We supposed that testis-sparing surgery can be a feasible therapeutic alternative to radical orchiectomy in patients with bilateral TGCTs in terms of improving the quality of life and continuing fertility and normal hormonal status with no medications. However, while the long-term effects are not yet known, this type of treatment should be perpormed in carefully selected cases with longlife expectancy.Key Words: Sycnhronous bilateral testis tumor, Intratubular germ cell neoplasia, Testis sparing surgery, Local radiotherapy     

Prevalence of pituitary adenomas in macroprolactinemic patients may be higher than it is presumed

One form of prolactin (PRL) is macroprolactin with high molecular mass. Many macroprolactinemic patients have no pituitary adenomas and no clinical symptoms of hyperprolactinemia, it is controversial whether macroprolactinemia is a benign condition that does not need further investigation and treatment. In this study, we aimed to compare macroprolactinemic patients (group I) with the true hyperprolactinemic patients (group II) for the presence of pituitary adenoma. We investigated 161 patients with hyperprolactinemia, whose magnetic resonance imaging records of the pituitary were taken. All patients were questioned for irregular menses, infertility and examined for galactorrhea. Patients were screened for macroprolactinemia by polyethylene glycol precipitation, and a recovery of ≤40% and normal monomeric PRL level was taken as an indication of significant macroprolactinemia. Of 161 patients with hyperprolactinemia, 60 (37.26%) had macroprolactinemia. PRL levels of group II were lower than those of group I (P = 0.011), although monomeric PRL levels of group II were higher than those of group I (P = 0.0005). Of 60 macroprolactinemic patients, 16 (26.7%) had pituitary adenomas. The prevalence of pituitary adenomas was lower in group I, compared with group II (P = 0.0005). No significant differences were found between the prevalences of irregular menses and infertility of group I and II (P = 0.084, P = 0.361). Prevalence of galactorrhea in group I was lower than that in group II (P = 0.048). Prevalence of pituitary adenomas in macroprolactinemic patients is lower compared with the true hyperprolactinemic patients, but may be higher than that found in other recent studies and in the general population.