Primary antibody deficiencies in Turkey: molecular and clinical aspects.

Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n = 4), CD40L (n = 1), ICOS (n = 1), IGHM (n = 1), and TCF3 (n = 1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2-10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.

Clinical and demographic features of hidradenitis suppurativa: a multicentre study of 1221 patients with an analysis of risk factors associated with disease severity.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, relapsing and debilitating inflammatory disease associated with profound morbidity. AIM: In this multicentre study, we investigated the demographic and clinical features of HS, and determined risk factors of disease severity. METHODS: In total, 1221 patients diagnosed with HS from 29 centres were enrolled, and the medical records of each patient were reviewed. RESULTS: The mean age of disease onset was 26.2 ± 10.4 years, and almost 70% (n = 849) of patients were current or former smokers. Mean disease duration was 8.9 ± 8.4 years with a delay in diagnosis of 5.8 ± 3.91 years. Just over a fifth (21%; n = 256) of patients had a family history of HS. The axillary, genital and neck regions were more frequently affected in men than in women, and the inframammary region was more frequently affected in women than in men (P < 0.05 for all). Acne (40.8%), pilonidal sinus (23.6%) and diabetes mellitus (12.6%) were the most prevalent associated diseases. Of the various therapies used, antibiotics (76.4%) were most common followed by retinoids (41.7%), surgical interventions (32.0%) and biologic agents (15.4%). Logistic regression analysis revealed that the most important determinants of disease severity were male sex (OR = 2.21) and involvement of the genitals (OR = 3.39) and inguinal region (OR = 2.25). More severe disease was associated with comorbidity, longer disease duration, longer diagnosis delay and a higher number of smoking pack-years. CONCLUSIONS: Our nationwide cohort study found demographic and clinical variation in HS, which may help broaden the understanding of HS and factors associated with disease severity.

Effect of retinyl acetate on transglutaminase 2 activity in carcinogen treated rat liver.

Transglutaminase 2 (TG2) has been implicated in wound healing, cellular differentiation, apoptosis and cell survival. TG2 activity increases following acute and chronic liver injury; however, the role of TG2 in tumors, is controversial. TG2 is a retinoid-inducible enzyme. We investigated the effects of retinyl acetate (RA) on the activity and levels of TG2 during the initiation and promotion stages of liver cancer. p-Dimethylaminoazobenzene (p-DAB) was used as initiator and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) was used as promoter in our model of carcinogenesis. Rats were divided into four groups of 24: control, corn oil control, p-DAB + TCDD, and p-DAB + TCDD + RA. Six rats from each group were sacrificed at days 30, 60, 90 and 120. TG2 activity decreased in the p-DAB + TCDD treated group, but TG2 immunostaining scores did not change by days 90 and 120. Neither TG2 enzyme activity nor the immunostaining score of TG2 protein changed in the tissues of the p-DAB + TCDD + RA group by days 90 and 120. TG2 activity was not be ameliorated by RA during the initiation or promotion stages of carcinogen induced liver cancer.

An Abandoned Copper Mining Site in Cyprus and Assessment of Metal Concentrations in Plants and Soil.

Mining is an important source of metal pollution in the environment and abandoned mines are extremely restricted habitats for plants. Some plant species growing on metalliferous soils around mine tailings and spoil-heaps are metal-tolerant and accumulate high concentrations of metals. In this investigation, we aimed to perform a research in the CMC-abandoned copper mining area in Lefke-North Cyprus to assess the recent metal pollution in soil and plant systems. We collected 16 soil samples and 25 plant species from 8 localities around the vicinity of tailing ponds. Some concentrations of metals in soil samples varied from 185 to 1023 mg kg(-1) Cu, 15.2 to 59.2 mg kg(-1) Ni, 2.3 to 73.6 mg kg(-1) Cd and metals for plants ranged from 0.135 to 283 mg kg(-1) Cu, 0.26 to 31.2 mg kg(-1) Ni, 0.143 to 277 mg kg(-1) Cd. Atriplex semibaccata, Acacia cyanophylla, Erodium spp., Inula viscosa, Juncus sp., Oxalis pes-caprea, Pistacia lentiscus, Senecio vulgaris and Tragopogon sinuatus accumulated higher concentrations. BCF for Atriplex semibaccata was found very high, for this reason this plant can tentatively be considered as a hyperaccumulator of Cu and Cd, but it needs further investigation for its potential in phytoremediation.

Effects of variable courses of inguinal nerves on pain in patients undergoing Lichtenstein repair for inguinal hernia: preliminary results.

BACKGROUND: Problems due to damage to ilioinguinal and iliohypogastric nerves which have many variations following surgery for inguinal hernia cause additional work leave and delay in return to daily life. We aimed to compare outcomes of nerve identification and preservation with a careful dissection during Lichtenstein repair of inguinal hernia between normal courses of inguinal based nerves and variable courses of inguinal based nerves. METHODS: This is a prospective study and 116 adult male patients with primary inguinal hernia were operated between December 2009 and June 2010. The patients with a normal nerve trace identified on exploration were assigned into Group Normal Course and those with variable nerve course were assigned into Group Variable Course. These two groups were compared in terms of demographic features, preoperative and postoperative variables, return to work and daily routines, duration of fulfilling personal needs, visual analogue scores before and one and six months after surgery, four-point verbal-rank scale scores, numbness and patient satisfaction. RESULTS: Out of 116 patients, 70 (60.3%) had variable courses of the nerves and were assigned into the Group Variable Course and 46 (39.7%) had normal courses of the nerves and were assigned into Group Normal Course. A single stem for both nerves over spermatic cord (21.6%) and acute infero-lateral angulation of the Ilioinguinal nerve in close contact with and parallel to the Superficial Inguinal Ring fibers at exit (15.5%) were the most observed variations. Duration of surgery was significantly longer in Group Variable Course (p <0.001). Numbness was also slightly higher in this group one month after surgery. This difference nearly disappeared six months after surgery. CONCLUSION: Although careful and gentle exploration increases the duration of surgery and early neuropraxia, identification and preservation of nerves during surgery for inguinal hernia help to achieve similar outcomes in both patients with a normal course of nerves and those with a variable course of nerves.

Positive inotropic, positive chronotropic and coronary vasodilatory effects of rat amylin: mechanisms of amylin-induced positive inotropy.

Even though there are a few studies dealing with the cardiac effects of amylin, the mechanisms of amylin-induced positive inotropy are not known well. Therefore, we investigated the possible signaling pathways underlying the amylin-induced positive inotropy and compared the cardiac effects of rat amylin (rAmylin) and human amylin (hAmylin).Isolated rat hearts were perfused under constant flow condition and rAmylin or hAmylin was infused to the hearts. Coronary perfusion pressure, heart rate, left ventricular developed pressure and the maximum rate of increase of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease of left ventricle (-dP/dtmin) were measured.rAmylin at concentrations of 1, 10 or 100 nM markedly decreased coronary perfusion pressure, but increased heart rate, left ventricular developed pressure, +dP/dtmax and -dP/dtmin. The infusion of H-89 (50 µM), a protein kinase A (PKA) inhibitor did not change the rAmylin (100 nM)-induced positive inotropic effect. Both diltiazem (1 µM), an L-type Ca2+ channel blocker and ryanodine (10 nM), a sarcoplasmic reticulum (SR) Ca2+ release channel opener completely suppressed the rAmylin-induced positive inotropic effect, but staurosporine (100 nM), a potent protein kinase C (PKC) inhibitor suppressed it partially. hAmylin (1, 10 and 100 nM) had no significant effect on coronary perfusion pressure, heart rate and developed pressure, +dP/dtmax and -dP/dtmin.We concluded that rAmylin might have been produced vasodilatory, positive chronotropic and positive inotropic effects on rat hearts. Ca2+ entry via L-type Ca2+ channels, activation of PKC and Ca2+ release from SR through ryanodine-sensitive Ca2+ channels may be involved in this positive inotropic effect. hAmylin may not produce any significant effect on perfusion pressure, heart rate and contractility in isolated, perfused rat hearts.

Interleukin-10 gene transfection of donor pancreas grafts protects against rejection after heterotopic pancreas transplantation in a rat model.

OBJECTIVE: The aim of this study was to assess the effect of immunoregulatory cytokine interleukin-10 (IL-10) gene therapy on pancreas tissue rejection in a heterotopic pancreas transplantation model. BACKGROUND: Modulation of inflammatory responses by anti-inflammatory cytokines (e.g., IL-10) has been suggested to minimize organ rejection. In this context, modulation of cytokines using gene therapy could be a new therapeutic modality in preventing organ rejection. METHODS: The study was performed using male inbred Wistar rats as recipients and Sprague-Dawley rats as donors. 24 h before transplantation, groups of rats, named IL-10 (n = 20) and green fluorescent protein (GFP, n = 20), were injected with viral vectors Ad5CMVhIL10 or Ad5CMVGFP. Sham-operated rats (n = 20) underwent saline injection only before transplantation. The pancreatic tissue from each of these donor rats was subsequently transplanted into the corresponding groups of streptozotocin-induced diabetic recipient rats. Recipients were thus transfected with either IL-10 (n = 20), GFP-only carrying viral vectors (n = 20) or no viral vectors (normal saline, n = 20). A selected number of animals from each recipient group (n = 5) was sacrificed at weekly intervals for 3 weeks and some were further followed up to 12 weeks before sacrifice. Histological assessment of the pancreatic tissue was made based on rejection and GFP expression. Blood glucose levels were checked daily in all groups until sacrifice. Upon sacrifice, serum cytokine and insulin levels were measured. Histopathological correlations between blood glucose levels, serum insulin levels and serum IL-10 levels were made. RESULTS: IL-10 gene therapy significantly attenuated pancreas rejection compared to controls, provided more normal blood glucose levels and elevated plasma insulin levels. Upon assumed natural deactivation of transferred viruses after 4 weeks, differences between groups in terms of rejection, blood glucose and insulin levels disappeared. CONCLUSION: These findings suggest that IL-10 gene therapy significantly reduced pancreas rejection.

Massive ovarian edema: a case report.

Massive ovarian edema is considered a non-neoplastic lesion characterized by a tumor-like enlargement of one or occasionally both ovaries secondary to an accumulation of edema fluid within the stroma. It is an uncommon entity that usually leads to oophorectomy as an unnecessary treatment in children, adolescents and young women. A diagnostic wedge resection with subsequent frozen section is essential. A definitive diagnosis of massive ovarian edema can not be made on preoperative imaging. In this article a case of massive ovarian edema in a 15-year-old female thought to be a solid neoplasm in the preoperative period is described.

Sclerosing stromal tumor of the ovary associated with Meigs' syndrome: a case report.

Sclerosing stromal tumors of the ovary are distinct, but rare benign neoplasms. These tumors appear solid and are very vascular giving the impression of malignant tumors. They occur mostly in young women. Morphologically they have distinct characteristics which differentiate them from other stromal tumors. Benign ovarian tumors associated with Meigs' syndrome are rare. In this article a case of ovarian sclerosing stromal tumor associated with Meigs' syndrome in a 17-year-old women is described and the differential diagnosis is also discussed.