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

MDCT: Angiography of anatomical variations of the celiac trunk and superior mesenteric artery

The aim of this study was to detect and describe the existence and incidence of anatomical variations of the celiac trunk and superior mesenteric artery. The study was conducted on 150 persons, who underwent abdominal Multi- Detector Computer Tomography (MDCT) angiography, from April 2010 until November 2012. CT images were obtained with a 64-row MDCT scanner in order to analyze the vascular anatomy and anatomical variations of the celiac trunk and superior mesenteric artery. In our study, we found that 78% of patients have a classic anatomy of the celiac trunk and superior mesenteric artery. The most frequent variation was the origin of the common hepatic artery from the superior mesenteric artery (10%). The next variation, according to frequency, was the origin of the left gastric artery direct from the abdominal aorta (4%). The arc of Buhler as an anastomosis between the celiac trunk and superior mesenteric artery, was detected in 3% of cases, as was the presence of a common trunk of the celiac trunk and superior mesenteric artery (in 3% of cases). Separate origin of the splenic artery and the common hepatic artery was present in 2% of patients. The MDCT scanner gives us an insight into normal anatomy and variations of the abdominal blood vessels, which is very important in the planning of surgical interventions, especially transplantation, as well as in the prevention of complications due to ischemia

Predicting the survival probability of functional neuroendocrine tumors treated with peptide receptor radionuclide therapy: Serbian experience

IntroductionPeptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment.MethodologyWe retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a non-progression group (n=33). Clinical data were compared between the two groups.ResultsA total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p<0.05), functional tumors (p<0.05), absolute neutrophil count (p<0.05), neutrophil-lymphocyte ratio-NLR (p<0.05), C-reactive protein-CRP (p<0.05), CRP/Albumin (p<0.05), alanine aminotransferase-ALT (p<0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p<0.001), age (p<0.05), CRP (p<0.05), and ALT (p<0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16 months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively.ConclusionThe study’s results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly

Bacterial Flora Play Important Roles in Acute Dextran Sulphate Sodium-Induced Colitis But Are Not Involved in Gal-3 Dependent Modulation of Colon Inflammation

An altered immune response to normal gut microflora is important for the pathogenesis of ulcerative colitis (UC). Galectin- 3 (Gal-3) is an endogenous lectin that plays an important pro-inflammatory role in the induction phase of acute colitis by promoting activation of the NLRP3 infl ammasome and production of IL-1β in macrophages. By using dextran sulphate sodium (DSS) induced colitis, a well-established animal model of UC, we determined whether Gal-3 affects the function of colon infiltrating macrophages by interfering with intestinal microfl ora. Our results showed that genetic deletion of Gal-3 significantly attenuates DSS-induced colitis by down-regulating infiltration of phagocytic cells (neutrophils, macrophages and dendritic cells) in colon tissue of DSS-treated mice, and this correlated with differences in bacterial flora of the gut. Antibiotic treatment attenuates DSS-induced colitis in WT and Gal-3-/- mice without affecting differences between the groups. In conclusion, Gram negative bacterial flora play an important role in DSS-induced acute colitis of mice but are not involved in Gal-3 dependent modulation of colon inflammation

Acute chemoradiotherapy toxicity in cervical cancer patients

During radiotherapy treatment for cervical cancer, up to 84% of patients exhibit some form of acute radiation toxicity (ART). The primary aim of this clinical study is to determine the impact of angiotensin-converting enzyme (ACE) inhibitors, β-blockers and other risk factors such as the patient’s anatomical characteristics on ART emergence in patients with locally advanced cervical cancer treated by chemoradiotherapy. This is a combination of two nested case–control studies within the cohort of patients with locally advanced cervical cancer based on the analysis of potential risk factors for the onset of ART in patients treated with 3D conformal radiotherapy (3D-CRT) and 2D conventional radiotherapy (2D-RT), prospectively followed up from January 2017 to September 2018 in a tertiary care hospital. The ACE inhibitors and bladder volume were identified as factors that significantly affect the occurrence of ART in patients treated with 3D-CRT. In patients treated with 2D-RT, the factors that significantly affect the occurrence of ART were ACE inhibitors, body mass index (BMI), brachytherapy rectal and bladder dose. This study has shown that BMI, radiation dose received by the bladder and rectum are of exceptional importance for the occurrence of the ART and also that therapy with ACE inhibitors was associated with the decreased chances of the ART

Morphology of Human Nucleus Accumbens Neurons Based on the Immunohistochemical Expression of Gad67

The nucleus accumbens is a part of the ventral striatum along with the caudate nucleus and putamen. The role of the human nucleus accumbens in drug addiction and other psychiatric disorders is of great importance. The aim of this study was to characterize medium spiny neurons in the nucleus accumbens according to the immunohistochemical expression of GAD67

Mesenchymal stem cells attenuate acute liver injury by altering ratio between interleukin 17 producing and regulatory natural killer T cells.

Mesenchymal stem cells (MSCs) are, due to immunomodulatory characteristics, considered as novel agents in the treatment of immune-mediated acute liver failure. Although it is known that MSCs can regulate activation of T lymphocytes, their capacity to modulate function of neutrophils and natural killer T (NKT) cells, major interleukin (IL) 17-producing cells in acute liver injury, is still unknown. By using 2 well-established murine models of neutrophil and NKT cell-mediated acute liver failure (induced by carbon tetrachloride and α-galactoceramide), we investigated molecular and cellular mechanisms involved in MSC-mediated modulation of IL17 signaling during acute liver injury. Single intravenous injection of MSCs attenuate acute hepatitis and hepatotoxicity of NKT cells in a paracrine, indoleamine 2,3-dioxygenase (IDO)-dependent manner. Decreased levels of inflammatory IL17 and increased levels of immunosuppressive IL10 in serum, reduced number of interleukin 17-producing natural killer T (NKT17) cells, and increased presence of forkhead box P3 + IL10-producing natural killer T regulatory cells (NKTregs) were noticed in the injured livers of MSC-treated mice. MSCs did not significantly alter the total number of IL17-producing neutrophils, CD4+, and CD8 + T lymphocytes in the injured livers. Injection of mesenchymal stem cell-conditioned medium (MSC-CM) resulted with an increased NKTreg/NKT17 ratio in the liver and attenuated hepatitis in vivo and significantly reduced hepatotoxicity of NKT cells in vitro. This phenomenon was completely abrogated in the presence of IDO inhibitor, 1-methyltryptophan. In conclusion, the capacity of MSCs to alter NKT17/NKTreg ratio and suppress hepatotoxicity of NKT cells in an IDO-dependent manner may be used as a new therapeutic approach in IL17-driven liver inflammation. Liver Transplantation 23 1040-1050 2017 AASLD

Mesenchymal stem cells attenuate liver fibrosis by suppressing Th17 cells - an experimental study.

This study investigates molecular and cellular mechanisms involved in mesenchymal stem cell (MSC)-mediated modulation of IL-17 signaling during liver fibrosis. Mice received CCl4 (1 μl/g intraperitoneally) twice/week for 1 month. MSCs (1 × 106 ), or MSC-conditioned medium (MSC-CM), were intravenously injected 24 h after CCl4 and on every 7th day. Liver fibrosis was determined by macroscopic examination, histological analysis, Sirius red staining, and RT-PCR. Serum levels of cytokines, indoleamine 2,3-dioxygenase (IDO), and kynurenine were determined by ELISA. Flow cytometry was performed to identify liver-infiltrated cells. In vitro, CD4+ T cells were stimulated and cultured with MSCs. 1-methyltryptophan was used for inhibition of IDO. MSCs significantly attenuated CCl4 -induced liver fibrosis by decreasing serum levels of inflammatory IL-17, increasing immunosuppressive IL-10, IDO, and kynurenine, reducing number of IL-17 producing Th17 cells, and increasing percentage of CD4+ IL-10+ T cells. Injection of MSC-CM resulted with attenuated fibrosis accompanied with the reduced number of Th17 cells in the liver and decreased serum levels of IL-17. MSC-CM promoted expansion of CD4+ FoxP3+ IL-10+ T regulatory cells and suppressed proliferation of Th17 cells. This phenomenon was completely abrogated in the presence of IDO inhibitor. MSCs, in IDO-dependent manner, suppress liver Th17 cells which lead to the attenuation of liver fibrosis

MDCT angiography of anatomical variations of the celiac trunk and superior mesenteric artery

The aim of this study was to detect and describe the existence and incidence of anatomical variations of the celiac trunk and superior mesenteric artery. The study was conducted on 150 persons, who underwent abdominal Multi- Detector Computer Tomography (MDCT) angiography, from April 2010 until November 2012. CT images were obtained with a 64-row MDCT scanner in order to analyze the vascular anatomy and anatomical variations of the celiac trunk and superior mesenteric artery. In our study, we found that 78% of patients have a classic anatomy of the celiac trunk and superior mesenteric artery. The most frequent variation was the origin of the common hepatic artery from the superior mesenteric artery (10%). The next variation, according to frequency, was the origin of the left gastric artery direct from the abdominal aorta (4%). The arc of Buhler as an anastomosis between the celiac trunk and superior mesenteric artery, was detected in 3% of cases, as was the presence of a common trunk of the celiac trunk and superior mesenteric artery (in 3% of cases). Separate origin of the splenic artery and the common hepatic artery was present in 2% of patients. The MDCT scanner gives us an insight into normal anatomy and variations of the abdominal blood vessels, which is very important in the planning of surgical interventions, especially transplantation, as well as in the prevention of complications due to ischemia