Could immune cells be associated with nephropathy in Fabry disease patients?

BACKGROUND: In Fabry Disease (FD), although the primary factor initiating kidney damage is glycosphingolipid accumulation, secondary conditions such as increased inflammation and fibrosis may cause this damage to progress. These processes may be induced by immune cells. Therefore, we aimed to investigate the peripheral lymphocyte subgroup analysis of the patients with FD and compare these results with healthy individuals. In addition, we performed T, B, NK, and plasma cell analyses in kidney biopsy materials and compared these kidney biopsy results with the biopsy results of patients whose kidney functions were impaired after 4 years of regular ERT. MATERIALS AND METHODS: 18 FD and 16 healthy individuals were included in the study. T-B lymphocyte and NK-cell populations were determined. We performed kidney biopsies (KBx) on 13 patients with FD prior to ERT. Of these, 4 patients had rebiopsy after 4 years of regular ERT. Immunohistochemical staining was performed to define immune cell infiltration. RESULTS: There was no statistically significant difference in terms of total, helper and cytotoxic T-lymphocyte and CD3-CD16+CD56+ natural killer (NK)-cell count (p = 0.20; p = 0.12; p = 0.76; p = 0.75, respectively).According to KBx findings prior to ERT, all patients had interstitial fibrosis (IF), podocyte vacuoles (PV), and podocyte inclusion (PI), CD3, CD4, CD8, CD16, and CD56 positivity at different levels. None of the patients had CD19, CD20, and CD138 positivity at the first biopsies. When we compared the first and the second KBx results of the two progressors, we also demonstrated that CD3+4+T-cells infiltration remained the same, whereas CD8+T cells, CD16+ and 56+NK-cells infiltration were significantly decreased. In contrast, CD20+B cells and CD138+plasma cell infiltration were significantly increased despite 4 years of ERT (15 fold and sixfold, respectively). The CD20+B and CD138+ plasma cells and IF were positively correlated with proteinuria. CONCLUSIONS: The progression of FD nephropathy and proteinuria is increased despite a long-term ERT. Immune cells, primarily B and plasma cells, might cause these unwanted consequences.

Evaluation of topical Dexmedetomidine administration in postlaminectomy epidural fibrosis rat model.

Epidural fibrosis is a challenging topic in spinal surgery. Numerous clinical and experimental studies have been focused on this issue to clarify problems faced in spinal procedures for the patient as well as the surgeon and find out new methodologies. Dense cytokines and growth factors which are released from inflammatory cells have been suggested to play a major role in the inception and progression of fibrosis. One of the most investigated and important actor in epidural fibrosis is assumed to be the transforming growth factor-1ß (TGF-1ß) formation. Studies showed that Dexmedetomidine (DEX) downregulates TGF-ß pathway with its anti-inflammatory and antioxidant effects. From this point of view, for the first time in the literature we try to observe if there will be an effect of topical DEX administration over epidural fibrosis in a rat model. We hypothesized that DEX might have preventive effects on epidural fibrosis via anti-inflammatory and antioxidant effects. Twenty-four adult male Wistar albino rats were randomly assigned to three groups (Topical DEX, Spongostan, Laminectomy). A total laminectomy was performed at the L3-L5 level and then the ligamentum flavum and epidural fat tissue were cleared away from the surgical site. Histopathological assessment was performed postoperatively after 4 weeks. Our study revealed that topical DEX administration may have effects on reducing epidural fibrosis. Topical DEX administration may be helpful in preventing epidural fibrosis after laminectomy in rats through multiple anti-inflammatory and antioxidant mechanisms as well as through TGF -1ß pathway.

Effect of non-genetic factors on milk yields traits in Simmental cows raised subtropical climate condition / Efeito de fatores não genéticos em produção de leite em gado simmental criado em condições climáticas subtropicais

The aim of this study was to identify non-genetic parameters affecting the milk yield traits of Simmental cows raised in subtropical climate conditions. Records on 1904 lactation events of Simmental cows (N=706) during 2001-2014 were included in this study. A generalized linear model was used to investigate the effect of non-genetic factors (calving year, season, and age; lactation number; birth type; and calf sex) on real milk yield (MY), adjusted 305-d lactation milk yield (305-d MY), adjusted mature-age 305-d lactation milk yield (305-d MAMY), lactation length (LL), and dry periods (DP). The MY, 305-d MY, 305-d MAMY, LL, and DP were 6413.04kg, 6060.30kg, 6871.21 kg, 329.88d, and 57.67d, respectively, in Simmental cows. The effects of calving year, birth type, and calf sex on MY were significant (P<0.05). Calving year, calving age, birth type, and calf sex had significant effects on 305-d MY (P<0.05). The 305-d MAMY was significantly affected by calving year, birth type, and calf sex (P<0.05). In conclusion, based on the findings of the present study, the milk yield traits of Simmental cows raised at subtropical climate conditions with ideal feeding and management strategies was in accordance with world standards.(AU)

O objetivo desse estudo foi identificar parâmetros não genéticos afetando características de produção de leite em vacas Simmental criadas em condições climáticas subtropicais. Registros em 1904 eventos de lactação de vacas Simmental (N=706) de 2001 a 2014 foram incluídos nesse estudo. Um modelo linear generalizado foi utilizado para investigar o efeito de fatores não genéticos (ano, estação, e idade de parto; número de lactação; tipo de nascimento; sexo do bezerro) em produção real de leite (MY), produção ajustada 305-d (305-d MY), produção ajustada madura 305-d (305-d MAMY), duração de lactação (LL), e períodos secos (DP). MY, 305-d MY, 305-d MAMY, LL, e DP foram 6413.04kg, 6060.30kg, 6871.21kg, 329.88d e57.67d, respectivamente, em vacas Simmental. Os efeitos de ano de parto, tipo de parto e sexo do bezerro em MY foram significantes (P<0.05). O 305-d MAMY foi significativamente afetado por ano de parto, tipo de parto e sexo do bezerro (P<0.05). Conclui-se que, baseado nos achados do presente estudo, a produção de leite de vacas Simmental criadas em condições climáticas temperadas com alimentação e estratégias de manejo ideais estava de acordo com padrões mundiais.(AU)

First report of carglumic acid in a patient with citrullinemia type 1 (argininosuccinate synthetase deficiency).

WHAT IS KNOWN AND OBJECTIVE: Carglumic acid is a structural analogue of human N-acetylglutamate, which has become an alternative therapeutic option for hyperammonaemia in organic acidaemias such as isovaleric acidaemia, methylmalonic acidaemia and propionic acidaemia, and it has been suggested in other urea cycle disorders such as ornithine transcarbamylase deficiency and carbamoyl phosphate synthetase 1 deficiency. CASE DESCRIPTION: A male newborn was diagnosed with citrullinemia after serum amino acid analyses revealed markedly elevated citrulline concentration together with homozygous p.Gly390Arg mutation in ASS1 gene. The ammonia concentration decreased and blood gas analysis normalized after peritoneal dialysis was performed for three days. Also, sodium benzoate, L-arginine and parenteral nutrition with glucose and lipid therapy were initiated. Until 1 year of age, low adherence to sodium benzoate therapy due to unpleasant taste caused hyperammonaemic episodes and obligated us to initiate carglumic acid (100 mg/kg/day) therapy. During treatment with carglumic acid, the median ammonia level was 45.6 µmol/L. The patient's treatment was switched from carglumic acid to sodium phenylbutyrate when he was 4.5 years old. Currently, the patient is 6.5 years old and remains under follow-up with sodium phenylbutyrate, L-arginine and protein-restricted diet. Plasma ornithine level was found to be significantly lower during the carglumic acid treatment compared to other treatments (P=.039). Also, glutamic acid was found to be higher during the sodium benzoate treatment period compared to other treatment periods (P=.024). WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first report describing the long-term use of carglumic acid in a patient with argininosuccinate synthetase deficiency.

Note: 3D printed spheroid for uniform magnetic field generation.

This article is focused on a novel and practical production method for a uniform magnetic field generator. The method involves building of a surface coil template using a desktop 3D printer and winding of a conducting wire onto the structure using surface grooves as a guide. Groove pattern was based on the parametric spheroidal helical coil formula. The coil was driven by a current source and the magnetic field inside was measured using a Hall probe placed into the holes on the printed structure. The measurements are found to be in good agreement with our finite element analysis results and indicate a fairly uniform field inside.

Evaluation of prehypertension and masked hypertension rate among clinically normotensive patients.

BACKGROUND: The present cross-sectional study was aimed to identify pre-hypertension and masked hypertension rate in clinically normotensive adults in relation to socio-demographic, clinical and laboratory parameters. METHODS: A total of 161 clinically normotensive adults with office blood pressure (OBP) <140/90 mmHg without medication were included in this single-center cross-sectional study. OBP, home BP (HBP) recordings and ambulatory BP monitoring (ABPM) were used to identify rates of true normotensives, true pre-hypertensives and masked hypertensives. Data on sociodemographic and clinical characteristics were collected in each subject and evaluated with respect to true normotensive vs. pre-hypertensive patients with masked hypertension or true pre-hypertensive. Target organ damage (TOD) was evaluated in masked hypertensives based on laboratory investigation. RESULTS: Masked hypertension was identified in 8.7% of clinically normotensives. Alcohol consumption was significantly more common in masked hypertension than in true pre-hypertension (28.6 vs. 0.0%, p = 0.020) with risk ratio of 2.7 (95% CI 1.7-4.4). Patients with true pre-hypertension and masked hypertension had significantly higher values for body mass index, waist circumference, systolic and diastolic OBP and HBP (p < 0.05 for each) compared to true normotensive subjects. ABPM revealed significantly higher values for day-time and night-time systolic and diastolic BP (p = 0.002 for night-time diastolic BP, p < 0.001 for others) in masked hypertension than true pre-hypertension. CONCLUSIONS: Given that the associations of pre-hypertension with TOD might be attributable to the high prevalence of insidious presentation of masked hypertension among pre-hypertensive individuals, ABPM seems helpful in early identification and management of masked hypertension in the pre-hypertensive population.

Survey of sulfites in wine and various Turkish food and food products intended for export, 2007-2010.

Surveys were carried out between 2007 and 2010 to determine the total levels of sulfites in 1245 samples of wines, dried apricots, dried vegetables, nuts, juices and purees, frozen foods and cereals containing dried fruit supplied by food inspectors and by food producers for testing or for export certification. Sulfite analysis of wine was carried out using the Ripper method with an LOQ of 5 mg l(-1) and for dried and other foods the Monier-Williams distillation procedure was employed with an LOQ of 10 mg kg(-1). In the survey all wines contained measurable sulfites, but with the exception of one sample of white wine they were otherwise below Turkish Food Codex limits of 160 mg kg(-1) for red wine, 210 mg kg(-1) to white wine and 235 mg kg(-1) for sparkling wine. None of the cereal products, frozen foods, juices or purees contained sulfites above 10 mg kg(-1). However, all dried apricot samples contained significant levels of sulfite with around 40% having levels exceeding the Turkish limit of 2000 mg kg(-1). Significant levels of sulfite were found in other samples of dried fruit with even a fruit and nut bar containing 1395 mg kg(-1) of sulfite, suggesting the dried fruit ingredients contained levels above regulatory limits.

Multiorgan involvement in a pediatric patient with hydatid disease.

Human Echinococcus infection still remains an important health problem in endemic regions. Herein, we report a 5-year-old boy with hydatid disease who has spleen, lung, kidney and liver involvement simultaneously. To our knowledge, there is no pediatric case with hydatid disease in the literature reporting simultaneous involvement of spleen, kidney, liver and lungs as in our case.

Combined liver-kidney transplantation and follow-up in primary hyperoxaluria treatment: report of three cases.

INTRODUCTION: Primary hyperoxaluria type-1 (PH1) is an autosomal recessive disorder caused by impaired activity of the hepatic peroxisomal alanine-glyoxilate aminotransferase, which leads to end-stage renal disease (ESRD) and requires combined liver-kidney transplantation (CLKT). Herein, we have reported 3 children diagnosed with PH1 who received CLKT. CASE 1: A 4.5-year-old boy with an elder brother diagnosed with PH1 was diagnosed during family screening when the sonography showed multiple calculi. Within 5 years he experienced flank pain, hematuria attacks, and anuric phases due to obstruction and received hemodialysis (HD) when ESRD appeared. CLKT was performed from his full-match sister at the age of 9.5. He is doing well at 5.5 years. CASE 2: A 7-year-old boy was admitted with polyuria, polydypsia, and stomach pain with renal stones on sonography. PD was instituted when serum creatinine and BUN levels were measured as high values. At the age of 10, CKLT was performed from his mother. His liver and renal function tests are well at 14 months after CKLT. CASE 3: A 2.5-year-old girl had attacks of dark urine without any pain; renal stones were imaged on sonography. She was diagnosed with PH1 and operated on several times due to obstruction. She received peritoneal dialysis and a cadaveric CLKT was performed when she was 9 years old. At the age of 16, she experienced chronic allograft nephropathy requiring HD and subsequent cadaveric donor renal transplantation at 1.5 years after initiation of HD. CONCLUSION: Herein, we have presented the favorable clinical outcomes of patients with CKLT to indicate the validity of this treatment choice for PH1.

Haemostatic actions of the folkloric medicinal plant extract Ankaferd Blood Stopper.

Ankaferd Blood Stopper (ABS), a standardized mixture of five plants, has been used historically as a haemostatic agent but its mechanism of action remains unknown. This study investigated the in vitro effects of ABS on haemostatic parameters. When added to plasma or serum, ABS induced the very rapid formation of a protein network and erythrocyte aggregation. The levels of coagulation factors II, V, VII, VIII, IX, X, XI, and XIII were not affected by ABS. Plasma fibrinogen activity and antigen levels were decreased following the addition of ABS, in parallel with the prolonged thrombin time. Total protein, albumin, and globulin levels decreased after the addition of ABS. Our findings suggest that ABS stimulates the formation of an encapsulated protein network that provides focal points for erythrocyte aggregation. ABS has the therapeutic potential to be used for the management of haemorrhage and this agent should be investigated further in clinical trials.

Phytochemical and antioxidant analysis of eight Hypericum taxa from Central Italy.

Eight taxa of the Hypericum spp. growing in Central Italy (Appennino Umbro-Marchigiano) were analyzed by HPLC-DAD for constituents quantitation, for antioxidant and free radical scavenging activities. H. perforatum subsp. veronense was the richest in phenolic compounds and hyperforin was detected for the first time in H. hircinum subsp. majus. Significant values of antioxidant activity were found in the investigated Hypericum taxa.

Solid pseudopapillary tumor of the pancreas as a cause of recurrent pancreatitis.

Solid pseudopapillary tumor (SPT) of the pancreas is a rare pancreatic tumor mostly seen in young women. We here report a twelve-year-old girl presenting with recurrent attacks of pancreatitis. No history of a systemic disease, trauma, drug usage or infection was present. All other etiologic factors like familial, hypertriglyceridemia, hypercalcemia, cystic fibrosis, medications were excluded. On abdominal ultrasound a heterogeneous mass was noticed at the tail of pancreas. Computerized tomography and magnetic resonance imaging proved that the mass was cystic. The mass was surgically removed. The diagnosis was pancreatic solid cystic papillary epithelial neoplasm. Although acute pancreatitis due to SPT was exceptionally reported, this is the first description of SPT leading to recurrent pancreatitis especially in children.

Lymphocytic colitis in a child with non-responsive celiac disease.

In celiac disease, symptoms usually improve with strict adherence to diet. Some patients however do not show improvement despite of diet therapy. We here report a girl with non-responsive celiac disease whose diarrhea did not improve despite of a gluten free diet. A 12-year-old girl with recurrent diarrhea and failure to thrive was diagnosed with celiac disease. After six months of gluten-free diet her symptoms persisted. Adherence to diet was considered as correct and complete by a dietitian evaluation and by anti-endomysial antibodies that had become negative. Treatment with pancreatic enzymes, metronidazole or lactose free diet did not improve her symptoms. Colonoscopy was performed and lymphocytic colitis was diagnosed on histology from colonic biopsies. After mesalamine therapy diarrhea ceased, and weight and height z scores increased. Lymphocytic colitis, which is uncommonly seen in children compared to adults, should be considered in nonresponsive celiac disease in children.

Effect of sex difference on platelet aggregation using an optical method in healthy subjects.

There are many studies reporting conflicting results of sex differences on various platelet functions. The purpose of this study was to investigate whether sex differences could affect platelet aggregation results using an optical method in healthy subjects. A total of 42 subjects, 21 males and 21 females, were included in the study. Platelet aggregation was induced by adenosine diphosphate (ADP; 5 microm), collagen (2 microg/ml), and epinephrine (10 microm). Optical aggregation was performed using a turbidometric method. In all platelet aggregation tests ADP, collagen and epinephrine were studied; there was no significant difference between females and males in platelet aggregation amplitudes and slopes. As a result, sex difference does not affect platelet aggregation performed with this optical method in healthy subjects. This result supports that there is no need for sex differentiation while composing control groups in platelet aggregation studies using the optical method.

Delayed gastric emptying in children with poor appetite.

BACKGROUND: In this study we aimed to evaluate gastric emptying time in children with poor appetite. METHODS: Anthropometrical measurements, daily energy intakes and gastric emptying times were determined in 36 children with poor appetite. The children were grouped as those with normal and delayed gastric emptying. These groups were then compared with respect to age and nutritional status. RESULTS: Malnutrition was found in 63.9% and gastric emptying was delayed in 58.3% of all cases. Children with delayed gastric emptying were significantly older and malnutrition was significantly higher in this group (7.2 +/- 3.1 vs 3.9 +/- 1.5 years, P: 0.001 and 81.0% vs 40.0%, P: 0.017, respectively). Daily mean energy intake was significantly lower than daily mean energy requirement in children with delayed and normal gastric emptying (P = 0.002 and 0.026 respectively). CONCLUSION: In children with poor appetite, probability of gastric motility disorders should be taken into consideration. Especially in children with failure to thrive at preschool and early school years gastric motility studies should be undertaken.

Prokinetic agents in childen with poor appetite.

BACKGROUND: Of the feeding disorders in children, poor appetite is probably one of the most common complaints notified by parents. Since gastric motility disorders may be the cause of this symptom, the aim of our study was to investigate the effect of prokinetics on children with poor appetite and delayed gastric emptying. METHODS: Poor appetite was graded by VAS at start and end of treatment. Delayed gastric emptying was assessed by 99mTechnetium tincolloid scintigraphy. Malnutrition was defined according to Waterlow criteria. After initial assessment behavioural feeding recommendations were provided and trimebutine given for 6 months. Scintigraphy was repeated during treatment. Anthropometrical measurements and daily energy intake calculations were performed monthly RESULTS: 21 children (M/F: 12/9) with a mean age of 7 +/- 3 years were studied. At the end of treatment, weight and height standard deviation scores improved significantly (-1.0 +/- 0.6 vs. -0.8 +/- 0.7, p = 0.008 and -1.1 +/- 1.0 vs. -0.8 +/- 0.9, p=0.003, respectively) and malnutrition rate decreased from 81% to 66.7%. Improvement of gastric emptying was shown in 11 out of 16 children but was not statiscally significant (P = 0.059). The visual analogue scale scores of appetite showed significant improvement with therapy (7.5 +/- 1.3 vs. 5.3 +/- 2.0, p = 0.012). CONCLUSION: Children with poor appetite who have delayed gastric emptying might benefit from prokinetic agent therapy combined with behavioural feeding recommendations.

The prevalence of liver function abnormalities in pediatric celiac disease patients and its relation with intestinal biopsy findings.

UNLABELLED: Abnormal liver function tests and liver damage are seen frequently with celiac disease. However, the pathogenesis of liver functions abnormality is not clearly understood. The aim of this study was to determine the frequency of abnormal liver functions in children with celiac disease and its relation with anthropometric measurements and severity of intestinal damage. PATIENTS AND METHODS: Twenty seven patients with celiac disease were included in the study. Anthropometric and laboratory examinations and intestinal biopsies were performed in all the patients. Mucosal lesions were classified according to the Marsh classification. Villous area, crypt height and mitotic count were measured morphometrically for all biopsy samples. RESULTS: The mean age of patients was 6 +/- 5 years on admission. Alanine aminotransferase levels were normal (group 1) or elevated (group 2) in 20 and 7 patients, respectively. The mean alanine aminotransferase levels were 22.0 +/- 7.2 in group 1 and 70.5 +/- 31.1 U/L in group 2 patients, (p < 0.001). Complaints, mean age, height for age, weight for height, serum albumin level, villous area, crypt height and mitotic count were not significantly different between the two groups. Similarly, the ratio of Marsh classification was not significantly different between the two groups. All patients were given a gluten-free diet. Serum aminotransferase values returned to normal after 7.4 +/- 2.7 months of a gluten-free diet. CONCLUSION: Abnormalities of liver functions are frequently seen in paediatric celiac disease patients. These abnormalities are not correlated with malnutrition and severity of intestinal mucosal lesions. Liver enzyme activities return to normal levels in a few months after gluten-free diet.

Evaluation of the effects of functional orthopaedic treatment on temporomandibular joints with single-photon emission computerized tomography.

The aims of this investigation were to evaluate the temporomandibular joints (TMJs) with single-photon emission computerized tomography (SPECT) in subjects treated with a mandibular advancement repositioning splint (MARS), and to compare the results with the total effect on dento-facial morphology. The study was undertaken on 17 Class II division 1 malocclusion subjects (nine males, eight females) with mandibular retrusion. Ten patients (five males, five females) formed the treatment group and seven (four males, three females) were used as the control. SPECT was performed only in the treatment group. Cephalometric evaluation showed significant increases in NAPog (P < 0.001) and SNB (P < 0.05) angles. Increased bone formation in theTMJs was analysed with the aid of pre- and post-treatment scintigraphic studies. The results indicate that new bone formation in the mandibular condyles seems to contribute to the increase in mandibular prognathism resulting from functional jaw orthopaedics.

Kinin receptors and their antagonists as novel therapeutic agents.

Plasma kinins are a family of peptides which play an important role in a variety of pathophysiological conditions. As a consequence of the progress in the area of kinin receptors, specific kinin receptor antagonists will be available in near future in order to provide more selective therapeutic modalities for the treatment of diseases such as asthma, cardiovascular diseases, inflammation, pain, etc. Although the initial observation leading to discovery of kinins has been performed in 1909, important progress on the development of specific kinin receptor antagonists has been made in last two decades. This review emphasizes the physiological functions of kinins along with their receptor subtypes and post-receptor events in the cellular signaling. In this article, the latest developments in the kinin receptor antagonists including nonpeptide ones have been reviewed.