VITAMIN D STATUS IN PATIENTS WITH MENTAL DISORDERS: A CROSS-SECTIONAL ANALYSIS OF SINGLE COHORT FROM ROUTINE PRACTICE.

CONTEXT: Clinical research suggests that vitamin D deficiency correlates with mental illnesses. OBJECTIVE: The aim was to prove that the patients from the psychiatric health care service in Serbia had higher vitamin D deficiency than patients from general practice. DESIGN: The study had a cross-sectional design. METHODS: The study included 47 patients aged 19 - 76 of both sexes with different mental disorders. We performed sample size calculation on available data for vitamin D deficiency in patients in health care facilities compared with the general population. The concentrations of vitamin D in serums were measured by HPLC (high performance/pressure liquid chromatography). RESULTS: The mean value of vitamin D (standard deviation) in the whole group of study subjects was 16.27(10.62) ng/mL; 68.1% of the patients had a deficiency of vitamin D (25(OH)D<20 ng/mL). The difference is statistically significant from expected proportion of people with vitamin D deficiency in general practice (p=0.040). Serum concentrations of 25(OH)D were significantly correlated with serum concentrations of phosphorus (ϱ=0.336, p=0.024) and sodium (ϱ=0.304, p=0.038). CONCLUSIONS: The patients of psychiatry health care had significantly higher frequency of vitamin D deficiency than expected. There is a significant association between serum levels of vitamin D, and phosphate and sodium.

CTLA-4 +49 A/G gene polymorphism in Croatian and Slovenian multiple sclerosis patients.

Polymorphisms in the CTLA-4 gene are known to be important in several autoimmune diseases, including multiple sclerosis (MS). Previous studies on the impact of CTLA-4 +49 A/G gene polymorphism have given contradictory results. We investigated the possible influence of this polymorphism on MS susceptibility and disease behaviour in Croatian and Slovenian populations. Genotyping was performed in 367 patients with MS and 480 control subjects using PCR-RFLP method. The G allele was present in 216 (58.9%) patients with MS vs. 282 (58.7%) healthy controls (P = 0.975, OR = 1.01, 95% CI = 0.76-1.32). No significant differences were observed in CTLA-4 +49 A or G allele distribution between patients and controls, indicating that this polymorphism does not influence susceptibility to MS in the surveyed populations. No correlation was observed between G allele carrier status and age at disease onset, disease course or severity.

Malignant biliary stenosis treated with two percutaneous stents--case report.

INTRODUCTION: During last three decades interventional radiology became most powerfull tool in palliative treatment of patients with malignant biliary stenosis. CASE REPORT: We report a case of 62-year-old patient with malignant biliary obstruction caused by recidivant tumor of common bile duct remnant with infiltration of previously created hepaticojejunostomia. Biliary decompression was achieved by placement of two self-expanding metallic stents. DISCUSSION: In presented patient, due to previous surgery percutaneous approach was mandatory. Also, considering the unresectability of recidivant lesion and poor prognosis, definitive, preferable internal biliary drainage was to be achieved. Therefore the placement of metallic self-expanding stent was the therapeutic method of choice. CONCLUSION: The aim of percutaneous minimally invasive radiological interventions is to achieve effective biliary decompression with internal bile drainage if possible.

Could the CCR5-Delta32 mutation be protective in SARS-CoV-2 infection?

Increasing evidence points to host genetics as a factor in COVID-19 prevalence and outcome. CCR5 is a receptor for proinflammatory chemokines that are involved in host responses, especially to viruses. The CCR5-delta32 minor allele is an interesting variant, given the role of CCR5 in some viral infections, particularly HIV-1. Recent studies of the impact of CCR5-delta32 on COVID-19 risk and severity have yielded contradictory results. This ecologic study shows that the CCR5-delta32 allelic frequency in a European population was significantly negatively correlated with the number of COVID-19 cases (p=0.035) and deaths (p=0.006) during the second pandemic wave. These results suggest that CCR5-delta32 may be protective against SARS-CoV-2 infection, as it is against HIV infection, and could be predictive of COVID-19 risk and severity. Further studies based on samples from populations of different genetic backgrounds are needed to validate these statistically obtained findings.

A case of lichen ruber planus in a patient with familial multiple sclerosis.

Multiple sclerosis and lichen ruber planus are clinically and histologically distinct complex disorders of putative autoimmune aetiology that are fairly commonly observed in isolation but rarely found in combination. Only two previous reports have described lichen skin disorders in association with multiple sclerosis. The present report describes the case of a 51-year-old Caucasian woman exhibiting both familial multiple sclerosis and lichen ruber planus. This combination may have occurred by chance or it might imply that these disorders share common mechanisms in their pathogenesis.

Protective effects of whey on rat liver damage induced by chronic alcohol intake.

In 2012, alcohol liver disease resulted in 3.3 million-5.9% of global deaths. This study introduced whey protection capacity against chronic alcohol-induced liver injury. Rats were orally administered to 12% ethanol solution in water (ad libitum, average 8.14 g of ethanol/kg body weight (b.w.)/day) alone or combined with whey ( per os, 2 g/kg b.w./day). After 6-week treatment, chronic ethanol consumption induced significant histopathological liver changes: congestion, central vein dilation, hepatic portal vein branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal necrosis. Ethanol significantly increased liver catalase activity and glutathione reductase protein expression without significant effects on antioxidative enzymes: glutathione peroxidase (GPx), copper-zinc-containing superoxide dismutase (CuZnSOD) and manganese-containing superoxide dismutase (MnSOD). Co-treatment with whey significantly attenuated pathohistological changes induced by ethanol ingestion and increased GSH-Px and nuclear factor kappa B (NF-κB) protein expression. Our results showed positive effects of whey on liver chronically exposed to ethanol, which seem to be associated with NF-κB-GPx signaling.

Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP.

It was reported that novel O, O'-diethyl-(S, S)-ethylenediamine- N, N'-di-2-(3-cyclohexyl) propanoate dihydrochloride (DE-EDCP) displayed in vitro antiproliferative activity on several human and mouse cancer cell lines, which was comparable to that of the prototypical anticancer drug cisplatin. In order to reveal its toxicity profile, acute and repeated-dose toxicity studies were performed in Naval Medical Research Institute (NMRI) Han mice. The intravenous LD50 values of DE-EDCP were found to be 95.3 and 101.3 mg/kg body weight in female and male mice, respectively. In the subacute toxicity study, DE-EDCP was administered intravenously at the doses of 15, 25, and 40 mg/kg/day for a period of 28 days. There were no adverse effects on general condition, growth, feed and water consumption, and hematological parameters. There was a significant increase in urea and alanine aminotransferase in female mice and aspartate aminotransferase and alkaline phosphatase in both genders in 40 mg/kg/day dose-treated group. The histopathological changes confined to the liver and kidney, but in other organs were not found. Satellite group revealed that changes in the kidney and liver were less pronounced, suggesting their reversibility. Interactions with DNA could also be of importance for understanding DE-EDCP toxic side effects. Hyperchromic effect obtained with ultraviolet-visible, suggested electrostatic interactions between DE-EDCP and calf thymus DNA. The toxicity testing of DE-EDCP was conducted to predict human outcomes.

Molecular characteristics and prognostic significance of Bcl-2/IgH gene rearrangement in Serbian follicular lymphoma patients.

Follicular lymphoma (FL) is characterized by the presence of a t(14;18) chromosomal translocation that results in overexpression of bcl-2 protein. Bcl-2/IgH gene rearrangement is detected in 80-90% of follicular lymphomas in Western countries. The aim of this study was to analyze the bcl-2/IgH rearrangement in FL lymphoma patients in Serbia, by PCR technique, correlate molecular findings with clinical characteristics and outcome and assess the prognostic significance of these rearrangements. One hundred-seven patients (median age, 54 years; male/female ratio:60/47) diagnosed with FL were included in the study. DNA samples were obtained from paraffin embedded lymphoid tissue of patients. Bcl-2/IgH rearrangement was assessed for the major breakpoint region (MBR), 5' MBR and the minor cluster region (mcr) breakpoints by PCR technique. We detected a t(14;18) in 81.3% (87/107) of patients. The distribution of bcl-2-IgH rearrangement was as follows: 88,5% (77/87) in MBR breakpoint, 10,35% (9/87) in 5' MBR, whereas mcr bcl-2-IgH rearrangement was observed in one patient (1.15%). No rearrangements were detected in remaining 20 patients (18.7%). This is the first analyses of the frequency of the bcl-2/IgH gene rearrangement in Serbian FL patients, as well as in Eastern European countries. There was no correlation between presence of bcl-2/IgH gene rearrangement and clinical outcome of disease. Incidence of bcl-2/IgH gene rearrangement in Serbian FL patients is relatively high, and similar to frequency in Western countries. Presence of this rearrangement in tumor tissue is not of prognostic significance.

Predictive value of prognostic indices in patients with follicular lymphomas.

PURPOSE: The aim of this study was to compare which of three indices--International Prognostic Index (IPI), Italian Lymphoma Intergroup (ILI) index, Follicular Lymphoma adapted International Prognostic Index (FLIPI)--is the most useful in predicting outcome in follicular lymphoma (FL) patients and to identify other clinical and laboratory prognostic factors that influence survival. PATIENTS AND METHODS: Clinical and prognostic studies were carried out in 99 patients with FL. RESULTS: The distribution of patients in IPI risk groups was 44.4%, 19.2%, and 36.4% of cases classified as low, intermediate, and high risk. According to ILI, low-, intermediate-, and high-risk scores were present in 34.3%; 27.3%, and 38.4% of FL patients. After applying the FLIPI index, the patients were divided into three risk groups: low (21.2% of cases), intermediate (39.4%), and high (39.4%) of FL patients. Survival curves demonstrated a high significant difference for the low- and high-risk group according to IPI and FLIPI (log rank=91.13 and 82.17 respectively; p < 0.0001). Difference in overall survival (OS) and failure-free survival (FFS) among low-, intermediate-, and high-risk groups according to ILI was statistically significant (log rank test p < 0.0001). CONCLUSION: All three indices are important tools for prognostic evaluation of FL patients, as well as useful in identifying FL patients with poor outcome. IPI and FLIPI classify patients into two risk groups (low/intermediate- and high-risk groups) with significance difference in OS and FFS, but ILI is more reliable in stratifying patients in low-, intermediate-, and high-risk groups.

Conversion of azathioprine to mycophenolate mofetil and chronic graft failure progression.

The purpose of the study was to evaluate the impact of conversion from azathioprine (AZA) to mycophenolate mofetil (MMF) on graft function in 35 renal transplant recipients with chronic allograft nephropathy (CAN). The immunosuppressive regimen originally consisted of AZA, cyclosporine (CsA), and prednisone (Pr). At the onset of the study (mean period = 39 posttransplant months), a graft biopsy was performed on all patients who were randomly divided into group 1 (n = 17) in whom MMF was introduced instead of AZA. The remaining 18 subjects (group 2) were maintained on the previous regimen. Two periods were analyzed: period I: 12 months before, and period II: 12 months after biopsy and therapy conversion. Graft function was assessed monthly by measurements of the 24-hour creatinine clearance (CCr). Analysis of variance (ANOVA) was used to compare the differences in CCr and proteinuria between the two groups. No difference was observed in the baseline characteristics, in the incidence of delayed graft function and acute rejection, or in the mean CsA dose. Pathohistological analysis revealed advanced CAN in the majority of patients in both groups. The morphological changes negatively correlated with graft function. The graft function showed parallel deterioration in the two groups; no significant difference was observed in the mean CCr values in the periods studied. Proteinuria was similar for both groups throughout the study. Conversion of AZA to MMF in recipients with CAN, albeit safe, was without significant benefit on the progression of chronic graft failure over the period of a year.

Kidney length in healthy members of Balkan endemic nephropathy families.

BACKGROUND: Kidney size may differ between healthy members of Balkan endemic nephropathy (BEN) and non-BEN families. The present study was designed to elucidate this, in comparison with values for BEN patients. METHODS: A total of 71 BEN patients (34 males, 64.4 ± 12.0 years), 74 healthy BEN family members (39 males, 49.1 ± 12.2 years), and 59 non-BEN family members (19 males, 49.2 ± 12.3 years) were involved. We measured the longest craniocaudal length and minimal parenchymal thickness on each kidney of all examined subjects using ultrasound. RESULTS: No significant difference was found between the kidney length of healthy subjects from BEN (11.0 ± 0.8 cm) and non-BEN families (10.9 ± 0.8 cm), but kidneys were significantly longer than in BEN patients (9.9 ± 1.3 cm). Minimal parenchymal thickness was similar in all three groups. When subjects from each group were divided according to estimated glomerular filtration rate (eGFR), kidney length of the healthy groups was significantly longer than in BEN patients both in stage 1 (p =0.039) and stage 2 (p =0.044) of chronic kidney disease. The parental history of BEN was not associated with kidney dimensions, eGFR, or urinary excretion of albumin and alpha1-microglobulin. CONCLUSION: Kidneys of BEN patients were significantly shorter than in healthy members of both BEN and non-BEN families, but no difference was found in kidney length and parenchymal thickness between healthy members of BEN and non-BEN families. No significant association was found between parental history of BEN and kidney size and function either in BEN patients or in healthy members from BEN families. Hippokratia 2015; 19 (4): 304-308.

Characterisation and preliminary lipid-lowering evaluation of Lactobacillus isolated from a traditional Serbian dairy product.

We investigated the potential probiotic properties of indigenous lactic acid bacteria (LAB) isolated from Serbian homemade cheese. Seventeen LAB strains were isolated and characterised using standard protocols. One of the strains showed several probiotic properties: survival at low pH and in bile salts solution, antimicrobial activity, susceptibility to antibiotics and adhesion to hexodecane. DNA analysis identified the isolate as Lactobacillus casei, hereafter named L. casei 5s. The lipid lowering effect of L. casei 5s was evaluated in vivo using a hyperlipidemic rat model. Orally administered L. casei 5s significantly decreased the elevated total serum cholesterol and triglycerides, and attenuated macro vesicular steatosis in the liver. Moreover, L. casei 5s improved the intestinal microbial balance in favour of lactobacilli, while decreasing the number of Escherichia coli cells. The bacteria were re-isolated and identified from the surface of the intestinal mucosa and from the faecal samples of treated animals, indicating adhesiveness and colonisation ability. The results of an acute oral toxicity study in mice and the absence of translocation to other organs demonstrated the safety of the strain. In conclusion, L. casei 5s demonstrated promising probiotic potential and might be a good candidate for more detailed investigations.

[News of Humalog and Humalog mix in the treatment of type 2 diabetes]. / Actualités de l'Humalog et des Humalog mix dans le traitement du diabète de type 2.

Fast-acting insulin analog (lispro insulin), as well as slow/fast-acting analog mixtures (NPL-lispro insulin) allow a better control of postprandial glycemia in type 1 and type 2 diabetic patients (35% mean reduction in area under curve for postprandial glycemia, 2 mmol/l reduction in postprandial glucose peak), as compared with regular insulin or conventional mixtures of NPH and regular insulin. Analog pharmacokinetics allow to procede to insulin injection immediately before meal, which is convenient for the patients. When used alone, lispro insulin has no impact on basal glycemia, whereas twice daily injections of NPL-lispro mixtures allow a 1.8 mmol/l mean reduction of basal glycemia, as compared with conventional mixtures, meaning a more specific effect of NPL intermediate insulin. Other premeal blood glucose levels (lunch and dinner) are not improved by lispro insulin. Most studies did not establish a clear reduction in HbA1c with insulin analogs. When this is the case, this reduction averages 1.5% and could be more frequently observed in studies dealing with type 2 diabetic patients. Finally, the reduced incidence of delayed hypoglycemic episodes, which is one of the most attractive effects of insulin analogs, was only reported in a minority of studies. Surprisingly, the reduction of hypoglycemia incidence with analogs was more frequently reported in type 2 diabetics than in type 1 patients. Thus fast-acting insulin analogs feature interesting characteristics, noteworthy immediate premeal injection and a better postprandial glucose control. However, it is established that the determination of diabetes complications (particularly microangiopathy) mostly relies on average glucose control and not solely on postprandial glycemia. Indeed, most studies suggest that insulin analogs are at least as efficient as conventional insulins on HbA1c, but possibly not more.

Treatment of type 1 diabetes with insulin lispro during Ramadan.

OBJECTIVE: To compare insulin lispro with regular human insulin with respect to blood glucose control and frequency of hypoglycaemia in patients with type 1 diabetes who wished to fast during the month of Ramadan. RESEARCH DESIGN AND METHODS: Insulin lispro or regular human insulin was given together with NPH insulin, twice daily before the morning and evening meals, for two weeks each in an open-label, randomised, cross-over design, and 64 patients completed the protocol. Blood glucose was self-monitored at fasting morning and evening, and 1-h and 2-h after the post-sunset meal on three consecutive days at the end of each treatment period. RESULTS: The 2-h blood glucose excursion after the post-sunset meal was significantly (p=0.026) lower with insulin lispro (2.50 +/- 0.46 mmol/l) than with regular human insulin (3.47 +/- 0.49 mmol/l). Daily insulin doses did not differ between treatments but compliance with recommended time of injection was better with insulin lispro. Hypoglycaemia incidence (insulin lispro, 15 (23.4%) patients; regular human insulin 31 (48.4%) patients; p=0.004) and frequency (insulin lispro, 0.70 +/- 0.19; regular human insulin 2.25 +/- 0.36 episodes/patient/30 days; p<0.001) were lower with insulin lispro. Five (22.7%) of the episodes during insulin lispro occurred during the nocturnal period compared with 27 (36.5%) of the episodes while on regular human insulin. CONCLUSIONS: Glycaemic control, measured by postprandial glycemic excursions, was improved and hypoglycaemia was significantly reduced with insulin lispro compared with regular human insulin. Patients with type 1 diabetes who insist on fasting during Ramadan may be better managed with insulin lispro.

Busulfan-induced loss of Ph chromosome in chronic myeloid leukemia.

We report a 44-yr-old female with Philadelphia chromosome positive chronic myeloid leukemia who was initially treated with busulfan, and clinical remission has been achieved. After 4 yr, low-dose busulfan therapy was started again and induced bone marrow aplasia. The patient spontaneously has recovered from aplasia, and complete cytogenetic remission with loss of Ph+ chromosome in bone marrow has been achieved. However, reverse-transcription-polymerase chain reaction analysis showed presence of the bcr-abl transcript in bone marrow.

Activities of antioxidant enzymes and formation of the glutathione adduct of hemoglobin (Hb ASSG) in epileptic patients with long-term antiepileptic therapy.

The activities of antioxidant enzymes (AOE) and amounts of glutathione adduct of Hb (Hb ASSG) in erythrocytes of chronic epileptic patients treated with mono or mixed therapy of phenobarbital (PB), carbamazepin (CBZ) and valproic acid (VPA), were evaluated and the results were compared with those for normal individuals. The activity of superoxide dismutase (SOD) was lowered for 40% to 60% in epileptic patients relative to normal controls. The lowest activity of SOD was found in patients treated with CBZ and PB. Activity of glutathione peroxidase (GSH-Px) was lowered comparing to the control from cca 15% in patients treated with PB to 50% in those treated with either CBZ alone or with CBZ in combination with PB. For the later two sub-groups of patients significantly lowered activities of catalase and glutathione reductase (cca 20% and 30-40%, respectively) were also characteristic. The highest amounts of Hb ASSG (cca 4% of the tota lHb) were found in hemolysates of patients with the lowest AOE levels i.e., in those treated with CBZ alone or with CBZ in combination with PB. In hemolysates of patients treated with PB, Hb ASSG represented 2.4% of the total Hb, while it was totally absent in those treated with VPA, although SOD and GSH-Px levels in erythrocytes of both of these sub-groups of patients were lowered to the same extent.

Synthesis of some new antianemics I. Iron pullulan complexes of pharmaceutical interest.

First experiments were performed in order to obtain a polynuclear iron(III) complex with pullulan, which could be applied in therapy of sideropenic anemia. Complete synthesis of the complex can be realized with oligomers of depolymerized pullulan at an average molar mass 8000-10,000 g.mol-1. Maximum iron contents of 51.4 mg.cm-3 is effected by pullulan depolymerizates (Mw approximately 9000 g.mol-1, [eta] = 0.085 dl.g-1) at 130 degrees C for 240 min, at pH = 10.5 and at an initial mass ratio Fe/ligand of 1:3. The effected concentrations and complex stability respond to requirements of pharmacological application of parenteral antianemic preparations.

Complete median nerve transection as a complication of carpal tunnel release with a carpal tunnel tome.

A 48 year-old right-hand-dominant man presented to our institution with paresthesia and loss of feeling along the median nerve distribution of the right hand 1 week after undergoing minimally open carpal tunnel release with the Biomet Indiana Tome at another hospital. At surgery, transection of the median nerve was discovered and repaired. This is the first report of a complete median nerve transection using the revised carpal tunnel tome with a single-pass technique.

The effect of a compulsory curriculum on ethical attitudes of medical students.

The purpose of the present study was to assess the influence of a compulsory curriculum on first-year medical students. The ethical attitude study was performed at the School of Medicine, University of Rijeka, Croatia. The samples consisted of 171 medical students (68 males and 103 females) interviewed at the beginning of the first year of studies. Some of them, namely 143 (56 males and 87 females) were interviewed again at the end of the same academic year. Data were analysed by applying factor analysis under principal component model and varimax criterion as the rotation model. The results clearly show that the current compulsory curriculum without formal ethical education has a limited influence on first-year medical students. That points to the obvious necessity to implement the medical ethics in the course of medical education.

HLA class I and class II polymorphism in the population of Rijeka, Croatia.

The aim of the study was to examine frequencies of HLA-A, -B, -DR antigens and haplotypes in population of Rijeka and to compare them with general Croatian and European populations. The subjects were 117 unrelated healthy blood donors. The antigens with the highest frequencies were: A2 (27.2%), A9 (16.3%), B5 (14.8%), B12 (11.8%), B18 (11.8%), DR5 (21.6%) and DR6 (13.8%). Comparison of HLA antigens frequencies has shown statistically significant difference in 1 antigen with Croatian population and in 8 antigens with European population. The HLA haplotypes with high frequencies included HLA-A2, B5 (6.84%), HLA-A2, B12 (6.84%), HLA-A2, B18 (6.84%), HLA-B12, DR2 (9.78%) and HLA-B18, DR5 (6.84%). The antigen B5 showed strongest association with DR5 (6.41%; LD = 1.30) as in general Croatian and in some European populations. The results have shown great diversity of HLA haplotypes in Rijeka population which can be the result of admixture with neighborhood immigrating populations during the history.