Association between risk factors, basal viral load, virus genotype and the degree of liver fibrosis with the response to the therapy in patients with chronic hepatitis C virus infection

© 2015, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved. Background/Aim. Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic dis-ease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with re-sponse to the therapy in patients with chronic heptitis C virus (HCV) infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV geno-type were analyzed. Methods. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for geno-type 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. Results. In the group of non-responding patients genotype 1 was repre-sented with 100%, while in the other groups, although predomi-nantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive sub-stances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse re-sponders and non-responders. Conclusion. The results of our study showed that the treatment outcome of chronic HCV infec-tion was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver

Nasal septum extramedullary plasmacytoma

Introduction. Plasmacytomas are malignant tumors characterized by abnormal monoclonal proliferation of plasma cells. They originate in either bone - solitary osseous plasmacytoma, or in soft tissue - extramedullary plasmacytoma (EMP). EMP represents less than 1% of all head and neck malignancies. Case report. We presented a case of EMP of the nasal septum in a 44-year-old male who had progressive difficulty in breathing through the nose and frequent heavy epistaxis on the right side. Nasal endoscopy showed dark red, soft, polypoid tumor in the last third of the right nasal cavity arising from the nasal septum. The biopsy showed that it was plasmacytoma. Bence Jones protein in the urine, serum electrophoresis, bone marrow biopsy, skeletal survey and other screening tests failed to detect multiple myeloma. This confirmed the diagnosis of EMP. The mass was completely removed via an endoscopic approach, and then, 4 week later, radiotherapy was conducted with a radiation dose of 50 Gray. No recurrence was noted in a 3-year follow- up period. Conclusion. EMP of the nasal cavity, being rare and having long natural history, represents a diagnostic and therapeutic challenge for any ear, nose and throat surgeon. Depending on the resectability of the lesion, a combined therapy is the accepted treatment

Dysplasia epiphysealis hemimelica: A case report

© 2014, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved. Introduction. Dysplasia epiphysealis hemimelica, also known as Trevor’s disease, is an extremely rare skeletal developmental disorder of unknown etiology, characterized by an osteocarti-laginous outgrowth of one or more epiphyses or of a tarsal bone during childhood. Case report. We presented a sporadic case of dysplasia epiphysealis hemimelica developed in the talus. A 6-year-old boy complained of swelling of his right ankle joint, with painful and reduced movements. Radiographies suggested excessive overgrowth of the dorsomedial aspect of the talus. The tumor was surgically excised and the gross and histological findings were consistent with those of osteochondroma. Conclusion. Dysplasia epiphysealis hemimelica is diagnosed by clinical, radiographic and histopathological examination. Early diagnosis is important for the condition to be treated before the deformity becomes disabling

Hypercalcemic type of small cell carcinoma of the ovary

© 2015, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved. Introduction. Extrapulmonary small cell carcinoma is a rare, prognostically bad tumor category. Primary, it can be localized in every organ, even in the ovary, where, due to its clinical specifici-ties, it represents a challenge in diagnosis, as well as in therapy. Small cell ovarian carcinoma (SCOC) is biologically very aggres-sive malignant tumor of unknown histogenesis. We presented a rare case of SCOC with hypercalcemia of aggressive course and fatal outcome in a postmenopausal woman at International Fed-eration of Gynecology and Obstetrics (FIGO) Ia stage. Case re-port. A 60-year-old woman, Caucasian, came to the doctor be-cause of discomfort in the lower abdomen and pain of greater in-tensity in last few days. Ultrasound examination and CT scan of the abdomen confirmed the presence of large adnexal masses of cystic-solid appearance with the largest diameter of 13 cm, regu-lar structure of the other gynecological organs, without verifying the existence of metastatic deposits. All the results of laboratory analysis gave normal values, except for calcium, which was ele-vated. Explorative laparotomy with complete hysterectomy, bi-lateral salpingo-oophorectomy, dissection of lymph nodes and omentectomy were conducted. Based on pathohistological analy-sis of the operative material, SCOC at FIGO Ia stage was diag-nosed. No complications were observed in a postsurgery period and after 10 days the patient was discharged in a good condition and with normal calcemia. The treatment was continued with concurrent radiotherapy and chemotherapy. However, in spite of overall treatment, the disease progressed, and the patient died of disseminated metastatic disease, 26 months after the diagnosis. Conclusion. Small cell carcinoma localized in the ovary is gener-ally a tumor category with bad prognosis depending on the stage of the disease

Expression of estrogen and progesterone receptors in subcutaneous endometriosis

Endometriosis is a clinical disorder defined by the presence of functional endometrial tissue outside the uterine cavity. Depending on the localization of the endometrial tissue related to the pelvis, the endometriosis can be classified either as intrinsic or extrinsic. The prevalence of endometriosis is difficult to determine. Statistical data show that endometriosis could be associated both with female infertility (20%) and pelvic pains (24%), while in 4.1% of affected women, endometriosis has asymptomatic forms. The total prevalence of endometriosis is estimated to be between 5-10%. A 35-year-old woman from Knic, Serbia, was admitted to the Obstetrics and Gynecology Clinic of the Clinical Center in Kragujevac for surgical treatment of a suspicious swelling in the pubic region. Following surgical intervention, a nut-sized tumor was removed and sent for both pathohistological and immunohistochemical analysis. The results confirmed the presence of subcutaneous endometriosis positive for both estrogen and progesterone receptors. Endometriosis is usually described as a steroid hormone-dependent change that resembles the eutopic endometrial tissue characteristic for the presence of both glandular and stromal tissues. Given the fact that endometrial lesions are estrogen-dependent tumors, a crucial factor in the development of endometriosis is a late exposure to the hormone, mostly estrogen. Spontaneous subcutaneous endometriosis is rarely observed, but it could be assumed if there is recurrent pelvic pain which intensifies during menstruation. Given the fact that endometriosis coexists with different autoimmune diseases, multidisciplinary approaches are required for its proper diagnosis

Exercise Attenuates Anabolic Steroids-Induced Anxiety via Hippocampal NPY and MC4 Receptor in Rats

The aim of our study was to evaluate the effects of chronic administration of nandrolone-decanoate (ND) or testosterone-enanthate (TE) in supraphysiological doses and a prolonged swimming protocol, alone and in combination with ND or TE, on anxiety-like behavior in rats. We investigated the immunohistochemical alterations of the hippocampal neuropeptide Y (NPY) and melanocortin 4 receptor (MC4R) neurons, as a possible underlying mechanism in a modulation of anxiety-like behavior in rats. Both applied anabolic androgenic steroids (AASs) induced anxiogenic effect accompanied with decreased serum and hippocampal NPY. The exercise-induced anxiolytic effect was associated with increased hippocampal NPY expression. ND and TE increased the number of MC4R, while the swimming protocol was followed by the reduction of MC4R in the CA1 region of the hippocampus. However, NPY/MC4R ratio in hippocampus was lowered by AASs and elevated by exercise in all hippocampal regions. An augmentation of this ratio strongly and positively correlated to increased time in open arms of elevated plus maze, in the context that indicates anxiolytic effect. Our findings support the conclusion that alterations in both hippocampal NPY and MC4R expression are involved in anxiety level changes in rats, while their quantitative relationship (NPY/MC4R ratio) is even more valuable in the estimation of anxiety regulation than individual alterations for both NPY and MC4R expression in the hippocampus

Sexual dimorphism of medium-sized neurons with spines in human nucleus accumbens

The nucleus accumbens is a limbic nucleus, representing part of the striatum body, and together with the caudate nucleus and putamen, it lies on the septum. The aim of this study was to examine morphological sexual dimorphism in spine density and also to undertake an immunohistochemical study of expression for estrogen and progesterone receptors in the medium-sized neurons in the nucleus accumbens. The research was conducted on twenty human brains of persons of both sexes, between the age of 20-75 years. The Golgi method was applied to determine the types and subtypes of neurons, morphologies of soma, dendrites and axons, as well as the relations between the cells and glial elements. The following were quantitatively examined: the maximum diameter of the neurons, the minimal diameter of the neurons, and the total length of the dendrites. The expression of receptors for estrogen and progesterone, their distribution and intensity were defined immunohistochemically. The parameters of the bodies of neurons in the shell and core of the nucleus accumbens were studied in both men and women. No statistically significant differences were found. Examination of the spine density showed statistical significance in terms of a higher density of spines in women. Immunohistochemically, in the female brain estrogen expression is diffusely spread in a large number of neurons; it is extra nuclear, of granular appearance and high intensity. In the male brain, expression of estrogen is visible and distributed over about one half of different types of neurons; it is extra nuclear, of granular appearance, mostly of middle and low staining intensity. Expression of progesterone in the female brain was very discreet and on a very small number of neurons; it was extra nuclear and with a weak staining intensity. Expression of progesterone in the male brain was distributed on a small number of neurons. It had a granular appearance, it was extra nuclear, with a very low staining intensity. Our results show differences in the morphology as well as expression of receptors for estrogen and progesterone on medium-sized neurons with spines in the nucleus accumbens of men and women

The Impact of Hippocampal Sex Hormones Receptors in Modulation of Depressive-Like Behavior Following Chronic Anabolic Androgenic Steroids and Exercise Protocols in Rats

The aim of this study was to evaluate alterations in depressive-like behaviors in rats following chronic administration of a supraphysiological dose of anabolic androgenic steroids (AASs) as well as exposure to a prolonged exercise protocol. The role of hippocampal sex hormones receptors in the modulation of depressive-like behavior was also assessed. A total of 48 male Wistar albino rats were divided into six groups: control, exercise (1 h/day, five consecutive days), nandrolone-decanoate (ND, 20 mg/kg/week, in a single dose), exercise plus ND, testosterone-enanthate (TE, 20 mg/kg/week, in a single dose), and exercise plus TE. After the 6-week protocols were complete, the rats underwent behavioral testing in the tail suspension test (TST). Rats were sacrificed for the collection of blood samples, to determine sex hormones levels, and isolation of the hippocampus, to determine [androgen receptors (AR) and estrogen receptors α (ERα)] expression. ND and TE treatment induced significant depressive-like behavior, opposing the antidepressant effect of exercise. Chronic TE administration elevated testosterone (T) and dihydrotestosterone (DHT) serum levels, and this was augmented by exercise. In contrast, ND and exercise alone did not alter T or DHT levels. There were no changes in serum estradiol levels in any of the groups. Immunohistochemical analysis showed that exercise reduced AR immunoreactivity in all hippocampal regions and increased the ERα expression in the CA1, dentate gyrus (DG), and total hippocampal sections, but not in the CA2/3 region. AASs administration increased AR expression in all hippocampal regions, although not the total hippocampal section in the TE group and did not significantly decrease ERα. The hippocampal AR/ERα expression index was lowered while parvalbumin (PV)-immunoreactivity was enhanced by exercise. AASs administration increased the AR/ERα index and reduced PV-immunoreactivity in the hippocampus. The number of PV-immunoreactive neurons negatively correlated with the antidepressant effects and the AR/ERα ratio. Our results suggest a potential role of the numerical relationship between two sex hormones receptors (stronger correlation than for each individual receptor) in the regulation of depressive-like behavior via the hippocampal GABAergic system in rats, which allow better understanding of the hippocampal sex hormones receptors role in modulation of depressive-like behavior

Gal-3 plays an important pro-inflammatory role in the induction phase of acute colitis by promoting activation of NLRP3 inflammasome and production of IL-β in macrophages

BACKGROUND AND AIMS: Galectin-3 [Gal-3] is an endogenous lectin with a broad spectrum of immunoregulatory effects: it plays an important role in autoimmune/inflammatory and malignant diseases, but the precise role of Gal-3 in pathogenesis of ulcerative colitis is still unknown. METHODS: We used a model of dextran sulphate sodium [DSS]-induced acute colitis. The role of Gal-3 in pathogenesis of this disease was tested by evaluating disease development in Gal-3 deficient mice and administration of Gal-3 inhibitor. Disease was monitored by clinical, histological, histochemical, and immunophenotypic investigations. Adoptive transfer was used to detect cellular events in pathogenesis. RESULTS: Genetic deletion or pharmacological inhibition of Gal-3 significantly attenuate DSS-induced colitis. Gal-3 deletion suppresses production of pro-inflammatory cytokines in colonic macrophages and favours their alternative activation, as well as significantly reducing activation of NOD-like receptor family, pyrin domain containing 3 [NLRP3] inflammasome in macrophages. Peritoneal macrophages isolated from untreated Gal-3(-/-) mice and treated in vitro with bacterial lipopolysaccharide or DSS produce lower amounts of tumour necrosis factor alpha [TNF-α] and interleukin beta [IL-1β] when compared with wild type [WT] cells. Genetic deletion of Gal-3 did not directly affect total neutrophils, inflammatory dendritic cells [DCs] or natural killer [NK] T cells. However, the total number of CD11c+ CD80+ DCs which produce pro-inflammatory cytokines, as well as TNF-α and IL-1β producing CD45+ CD11c- Ly6G+ neutrophils were significantly lower in colons of Gal-3(-/-) DSS-treated mice. Adoptive transfer of WT macrophages significantly enhanced the severity of disease in Gal-3(-/-) mice. CONCLUSIONS: Gal-3 expression promotes acute DSS-induced colitis and plays an important pro-inflammatory role in the induction phase of colitis by promoting the activation of NLRP3 inflammasome and production of IL-1β in macrophages