Evaluation of steroid therapy in COVID-19 patients; in the right dose at the right time to the right patients.

Background: Although there is still no universally accepted treatment agent, steroids have been administered chronologically at every dose and at every stage of the COVID-19 pandemic. Aim: We aimed to evaluate the clinical efficacy of high-dose steroid therapy and its effect on mortality in COVID-19 patients with severe pneumonia, severe Acute Respiratory Distress Syndrome (ARDS), and septic shock. Patients and Methods: : Patients with severe pneumonia, septic shock, and ARDS due to COVID-19 who were followed up in the intensive care unit were retrospectively reviewed. Results: The study population was divided into two groups; the methylprednisolone pulse group (MP) (n = 55) and the dexamethasone group (Dex) (n = 39). When the values before and after treatment were compared; there was a statistically significant increase in the neutrophil/lymphocyte ratio after treatment in the MP group (p = 0.006). Although it was not statistically significant in the MP group, There was a numerical increase in D-dimer levels (p = 0.28). Thromboembolic complications developed in 2 patients in the MP group. The mortality outcomes of the groups were statistically similar (p = 0.943). Conclusion: We recommend steroids use in the condition that it is indicated in the critically ill group with the poor general condition. Since there is no significant difference between high-dose pulse steroid treatment and standard treatment doses, we think that the risk of complications should not be taken into account and high doses should not be used.

Co-administration of apigenin with doxorubicin enhances anti-migration and antiproliferative effects via PI3K/PTEN/AKT pathway in prostate cancer cells.

Prostate cancer is one of the leading cancers in men, and new approaches are needed for its treatment. The aim of this study was to investigate the effect of co-administration of naturally occurring flavone apigenin and doxorubicin to androgen-insensitive prostate cancer cells. METHODS: The effect of the treatment on survival and migration of human PC3 cells was evaluated by MTT and scratch assay, respectively. Apoptosis and cell cycle distribution were detected by image-based cytometry. mRNA and protein expression were determined by real-time quantitative polymerase chain reaction and Western blot, respectively. RESULTS: Apigenin and doxorubicin dose-dependently inhibited cell survival, and co-administration of both agents significantly induced cell death via upregulating the mRNA expression of caspases, Bax and cytochrome c, and downregulating Bcl-XL. Combination therapy caused cell cycle arrest by upregulating the expression of p21 and p27. The treatment modality inhibited cell migration via downregulating Snail, Twist and MMPs in which doxorubicin was ineffective. Apigenin dephosphorylated Akt strongly, significantly suppressed ERK phosphorylation, and increased PTEN expression 4.5-fold. The combination of apigenin and doxorubicin inhibited PI3K and AKT phosphorylation more strongly than a single administration. CONCLUSIONS: Our data indicate that a combination of the natural flavone apigenin with doxorubicin might have a potential in treatment of castration-resistant prostate cancer.

The Effect of Tadalafil on Renal Fibrosis Induced by Ureteral Obstruction / Efecto del Tadalafil en la Fibrosis Renal Inducida por Obstrucción Uretral

ABSTRACT Objective: It has been reported that phosphodiesterase-5 (PDE-5) inhibitors improve kidney function during acute and chronic renal failure. This study aimed to determine the possible therapeutic effects of tadalafil, a specific PDE-5 inhibitor, on renal fibrosis induced by unilateral ureteral obstruction (UUO). Methods: Male Sprague-Dawley rats were used and randomly divided into three groups (n = 6) as sham-operated, UUO and tadalafil-treated (10 mg/72 hours, ig) UUO (UUO+T) groups. Unilateral ureteral obstruction was induced by complete ligation of the left ureter and 14 days after surgery creatinine clearance, urinary cyclic guanosine monophosphate (cGMP), renal alpha-smooth muscle actin (α-sma) and transforming growth factor βeta (TGF-β) levels, as well as histologic changes, were observed in all the animals. Results: Unilateral ureteral obstruction-induced renal fibrosis was confirmed by increased α-sma level, collagen deposition, tubular dilation, inflammatory cell infiltration and necrosis. An increased renal TGF-β level and decreased urinary cGMP level was also observed in obstructed animals in addition to reduced creatinine clearance. Tadalafil treatment, which restored the animals 'urinary cGMP level, significantly attenuated the fibrotic changes and TGF-β increase in their kidneys. Conclusion: This study suggests that tadalafil treatment ameliorates renal fibrosis by reducing TGF-β expression and may have important clinical relevance since tadalafil is currently used clinically to treat erectile dysfunction and pulmonary hypertension.

RESUMEN Objetivo: Se ha reportado que los inhibidores de la fosfodiesterasa-5 (PDE-5) mejoran las funciones renales durante la insuficiencia renal aguda y crónica. Este estudio tuvo por objetivo determinar los posibles efectos terapéuticos del tadalafil - un inhibidor específico de la PDE-5 - sobre la fibrosis renal inducida por una obstrucción ureteral unilateral (OUU). Métodos: Se utilizaron ratas machos Sprague-Dawley, divididas de manera aleatoria en tres grupos (n = 6): operación simulada, OUU y tratamiento con tadalafil (10 mg/72 horas, IG), y OUU (OUU+T). La obstrucción uretral unilateral fue inducida por una ligadura completa del uréter izquierdo y 14 días después de la cirugía, se observaron niveles de monofosfato de guanosina cíclico (GMP) urinario, alfa-actina de músculo liso (α-SMA), y factor de crecimiento transformante βeta (FCT-β), así como cambios histológicos en todos los animales. Resultados: La fibrosis renal inducida por obstrucción uretral unilateral fue confirmada por un aumento del nivel de α-SMA, deposición de colágeno, dilatación tubular, infiltración de células inflamatorias y necrosis. También se observó un aumento del nivel de FCT-β renal y una disminución del nivel de GMP urinario en los animales con obstrucción, además de una reducción del aclaramiento de la creatinina. El tratamiento con tadalafil, que restauró el nivel de GMP urinario de los animales, atenuó significativamente los cambios fibróticos y el aumento de FCT-β en los riñones. Conclusión: Este estudio sugiere que el tratamiento con tadalafil mejora la fibrosis renal al reducir la expresión de FCT-β y puede tener una importante relevancia clínica por cuanto el tadalafil se usa hoy día clínicamente para tratar la disfunción eréctil y la hipertensión pulmonar.

Increased serum levels of GDF-15 associated with mortality and subclinical atherosclerosis in patients on maintenance hemodialysis.

BACKGROUND/AIMS: Increased carotid intima-media thickness (CIMT) was shown to be an independent predictor of cardiovascular (CV) mortality in dialysis patients and the general population. Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor superfamily, is produced by cardiomyocytes and atherosclerotic lesions under stress conditions such as inflammation. We assessed associations between serum concentrations of GDF-15, mortality, and CIMT for subclinical atherosclerosis in hemodialysis (HD) patients. METHODS: A total of 87 patients on maintenance hemodialysis and 45 sex- and age-matched healthy controls were included in this prospective study. Serum GDF-15 levels were measured by ELISA. CIMT was assessed by Doppler ultrasonography. The association between serum GDF-15 levels and mortality was assessed using Cox regression analysis with serum levels categorized into two groups according to the median value (328.18 pg/ml). Patients were followed for 2 years and cause-specific and all-cause mortality were determined. RESULTS: The median level of serum GDF-15 was significantly higher in HD patients than controls [328 (198-522) vs. 176 (101-289) pg/ml, p < 0.01, respectively]. Serum GDF-15 levels were correlated to CIMT (r = 0.607, p < 0.001), C-reactive protein (CRP; r = 0.250, p = 0.010), HD duration (r = 0.376, p = 0.004), and serum albumin (r = - 0.156, p = 0.030). The multivariate analysis revealed that GDF-15 was found to be an independent variable of CIMT in HD patients. In the study, the serum GDF-15 level was an independent marker of all-cause of mortality when adjusted for age, CRP, and history of diabetes mellitus. CONCLUSION: The relationship between serum GDF-15, mortality, and carotid artery thickening suggests that GDF-15 may be a novel marker of atherosclerosis, inflammation, and malnutrition in HD patients.

Dysnatremia on intensive care unit admission is a stronger risk factor when associated with organ dysfunction.

AIM: Dysnatremia present at the time of intensive care unit (ICU) admission is associated with mortality. In this study, we investigated the epidemiology of dysnatremia present on ICU admission and the impact of organ dysfunction on the association between dysnatremia and mortality. We hypothesized that dysnatremia comorbid with organ dysfunction is associated with higher risk of mortality. METHODS: This retrospective study was conducted on all patients admitted to the International Hospital General ICU in Istanbul over a period of 6 years (2006-2011). Patients were classified, according to the most abnormal serum sodium values measured within 24 hours after ICU admission, into 7 groups as follows: normonatremia (135≤Na≤145 mmol/L), borderline hyponatremia (130≤Na<135 mmol/L), mild hyponatremia (125≤Na<130 mmol/L), severe hyponatremia (Na <125 mmol/L), borderline hypernatremia (145155 mmol/L). RESULTS: The total admitting patient were 1657. A total of 1060 patients' data were analyzed in this study. Sodium levels were normal in 637 (60.1%), hyponatremic in 367 (34.6%) and hypernatremic in 56 (5.3%) patients. Multivariate analysis showed that only SAPS II was associated with increased mortality (OR, 1.05 [95% confidence interval, 1.02-1.09]). The odds ratio (95% CI) of dysnatremia (Na <125 mmol/L and >150 mmol/L) for mortality was 4.37 (2.29-8.36) in patients with organ dysfunction (number of dysfunctional organs ≥1) (P<0.001). CONCLUSION: Below 125 and above 150 mmol/L sodium levels at ICU admission are risk factors for higher mortality rates in patients with comorbid organ dysfunction. The effect of dysnatremia on mortality is observed when organ dysfunction is present.

Benefits of the neutrophil-to-lymphocyte ratio for the prediction of gestational diabetes mellitus in pregnant women.

AIMS: There is growing consensus in the literature that inflammation plays a central role in the pathophysiology of obesity, Type 2 Diabetes Mellitus (T2DM), Gestational Diabetes Mellitus (GDM) and cardiovascular complications. Measuring the neutrophil-to-lymphocyte ratio (NLR) provides a simple inexpensive method for the assessment of inflammatory status. We investigated the predictive value of pre-procedural (before the oral glucose tolerance test (OGTT)) NLR on the development of GDM in pregnancy. METHODS: 42 women with GDM and 68 women without GDM were included in the study. Complete Blood Count and biochemical tests were followed by a diagnostic 4-point 100-g-OGTT within 2 weeks. GDM was diagnosed by the Carpenter and Coustan criteria. The NLR was calculated from the data. RESULTS: The mean NLR level was significantly higher in GDM women (3.00±0.83 vs. 2.26±0.43 p<0.001, respectively). In ROC analysis, NLR>2.93 had 76.2% sensitivity and 94.1% specificity in predicting GDM. Logistic regression analysis showed that elevated NLR (OR: 5.512, 95% CI: 1.352-22.475, p=0.017) was an independent variable for predicting GDM in pregnancy. CONCLUSIONS: An elevated NLR level is a powerful and independent predictor of GDM. The results of this study suggested that inflammation plays a central role in the pathogenesis of GDM.

Comparison of slime-producing coagulase-negative Staphylococcus colonization rates on vinyl and ceramic tile flooring materials.

This study investigated the colonization of slime-producing coagulase-negative Staphylococcus (CoNS) in 80 patient wards in Turkey (40 vinyl and 40 ceramic tile floors). A total of 480 samples that included 557 CoNS isolates were obtained. Slime production was investigated with the Christensen method and methicillin-susceptibility was tested by the disk-diffusion method. There was a significant difference in the percentage of slime-producing CoNS isolates on vinyl (12.4%) versus ceramic tile flooring (4.4%). From vinyl flooring, the percentage of slime producing methicillin-resistant CoNS (MRCoNS) (8.9%) was significantly higher than for methicillin-sensitive CoNS (MSCoNS) (3.6%), whereas there was no difference from ceramic tile flooring (2.5% MRCoNS versus 1.8% MSCoNS). The most commonly isolated slime-producing CoNS species was S. epidermidis on both types of flooring. It is concluded that vinyl flooring seems to be a more suitable colonization surface for slime-producing CoNS than ceramic tile floors. Further studies are needed to investigate bacterial strains colonized on flooring materials, which are potential pathogens for nosocomial infections.

Detection of coagulase activity in pathogenic Candida species.

The coagulase activities of various Candida spp were assessed using a classical tube test. A total of 125 clinical Candida isolates representing eight species (C. albicans, C. parapsilosis, C. tropicalis, C. glabrata, C. kefyr, Geotrichum candidum, C. krusei and C. guilliermondii) were incubated with rabbit, sheep or human plasma. After 24 h incubation, 29/64 (45.3%) C. albicans isolates and 23/61 (37.7%) non-albicans Candida strains were positive for coagulase in rabbit plasma, whereas 20/64 (31.2%) C. albicans and 6/61 (9.8%) non-albicans Candida isolates were positive for coagulase in sheep plasma. None of the tested Candida isolates reacted positively in human plasma. These results suggest that rabbit plasma is the most appropriate medium for detection of coagulase activity in Candida spp. Variations in coagulase production by Candida spp may be related to their pathogenicity. It is concluded that the laboratory detection of coagulase activity in clinical isolates of Candida spp may help the diagnosis of Candida-related infections.

Propofol reduces nitric oxide-induced apoptosis in testicular ischemia-reperfusion injury by downregulating the expression of inducible nitric oxide synthase.

BACKGROUND: The aim of the present study was to investigate the underlying mechanisms in the preventive effects of intravenous anesthetics on testicular ischemia-reperfusion injury. METHODS: Forty male Wistar Albino rats were randomly assigned to four groups of 10 rats each. Anesthesia was induced and maintained with thiopental in groups 1 and 2 and with propofol in groups 3 and 4. Groups 2 and 4 received left testicular ischemia (torsion) for 1 h and reperfusion (detorsion) for 24 h. Groups 1 and 3 (control groups) had no testicular torsion and detorsion. At 24 h of reperfusion, animals were killed and ipsilateral testes were removed for determination of tissue nitric oxide (NO) levels and immunohistochemical evaluation of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and apoptosis protease-activating factor 1 (APAF-1). RESULTS: Between groups 1 and 3, there were no differences in tissue NO levels and eNOS, iNOS, and APAF-1 expressions. iNOS and APAF-1 expressions were markedly increased in group 2, but these parameters were at the mild to moderate level in group 4 at 24 h of reperfusion. Also, elevated expression of iNOS was accompanied by a high NO production in group 2 compared with group 4. Although eNOS expressions were increased in both the groups (groups 2 and 4), there were no significant differences between these groups. CONCLUSIONS: Propofol as an anesthetic agent may attenuate germ cell-specific apoptosis and decrease NO biosynthases through downregulation of iNOS expression in an animal model of testicular torsion and detorsion.

The preventive effects of thiopental and propofol on testicular ischemia-reperfusion injury.

BACKGROUND: Testicular torsion is a urological emergency that requires immediate surgical intervention to prevent testicular damage. The aim of the study was to investigate the preventive effects of thiopental and propofol as anesthetics on testicular ischemia-reperfusion injury. METHODS: Forty male Wistar Albino rats were randomly assigned to four groups of 10 rats each. During 5 h, anesthesia was induced and maintained with thiopental in groups 1 and 2 and with propofol in groups 3 and 4. Groups 2 and 4 received left testicular ischemia (torsion) during 1 h and reperfusion (detorsion) during 4 h. Groups 1 and 3 (control groups) had no testicular torsion and detorsion. At the end of 5 h, animals were killed and both ipsilateral and contralateral testes were removed for histopathologic examination and measurement of tissue MDA (malondialdehyde) and NO (nitric oxide) levels. RESULTS: In the contralateral testes of all the groups, MDA and NO measurements were not different from ipsilateral testes of the control groups. Between the groups 1 and 3, there were no differences in MDA and NO levels. Although torsion/detorsion of testes in group 4 caused significantly increased levels of tissue MDA and NO values compared with group 3, ischemia-reperfusion in group 2 caused a further increase in these levels compared with group 4. The ipsilateral testes in the control groups did not show any morphological changes. Testicular torsion/detorsion in rats with thiopental anesthesia (group 2) caused significantly greater histopathologic injury levels than rats with propofol anesthesia (group 4). CONCLUSION: Our results suggest that propofol as an anesthetic agent may prevent testicular damage by scavenging reactive oxygen and nitrogen species and inhibiting lipid peroxidation in an animal model of testicular torsion and detorsion.

Infestation of the human intestine by the millipede, Nopoiulus kochii.

Specimens of the millipede, Nopoiulus kochii (Gervais) were seen in faeces and vomit of a 14-year-old boy residing in Oltu, Erzurum, Turkey. The patient complained of a burning sensation in his throat and stomach-ache. Physical examination revealed no pathological findings, and how the patient became infected was unknown. Anti-parasitic drugs (niclosamide, albendazole), which he had been taking intermittently for 2 years by the prescription of a physician, had not resolved the problem.

Nasopharyngeal carriage rate of Haemophilus influenzae in children aged 7-12 years in Turkey.

This study was undertaken to determine the nasopharyngeal carriage prevalence of Haemophilus spp. in children aged 7-12 years in Erzurum, Turkey. Three hundred randomly selected students from three regions with different socioeconomic properties were included in the study. Nasopharyngeal swabs taken from the students were streaked into selective media for Haemophilus spp. Isolated colonies were identified by macroscopic and microscopic examination and their X and V factor needs determined. Those identified as H. influenzae were serotyped by specific capsule antisera. Haemophilus spp. were recovered from 51 (17.0%), nine (3.0%) of which were H. influenzae type b (Hib), 30 (10.0%) H. influenzae non-type b, and 12 (4.0%) H. parainfluenzae. Results were evaluated by several risk factors such as age, gender, number of siblings, siblings attending a nursery, family smoking habits and family economic status.

A comparison of high-level aminoglycoside resistance in vancomycin-sensitive and vancomycin-resistant Enterococcus species.

The aim of this study was to investigate whether there was a significant difference in high-level aminoglycoside resistance (HLAR) between vancomycin-sensitive enterococci (VSE) and vancomycin-resistant enterococci (VRE). Vancomycin resistance was determined in 116 Enterococcus isolates using brain-heart infusion agar containing 6 micrograms/ml vancomycin. HLAR was determined by both standard agar screening and disk diffusion methods. Streptomycin and gentamicin were used as predictors of HLAR. Vancomycin resistance and HLAR were found in 17 (14.7%) and 41 (35.3%) of the Enterococcus strains, respectively. HLAR was found in 11 of 17 VRE and 30 of 98 VSE strains. HLAR in VRE strains was significantly higher than in VSE. More enterococcal strains were found to be resistant to both gentamicin and streptomycin (29) than to gentamicin (one) or streptomycin (11) alone. The HLAR rate in VRE was two-fold higher than in VSE. The synergistic bactericidal effect of aminoglycosides and beta-lactam or glycopeptide antibiotics is lost if there is high-level resistance to aminoglycosides.

Sero-epidemiology of tetanus antibody among the children in eastern Turkey.

The aim of the study was to determine immunity status of children to tetanus, and to assess the Expanded Programme on Immunization. A total of 840 children aged 0-71 months were randomly selected from three provinces in eastern Turkey by using cluster-sampling method. Blood samples were collected and enzyme linked immunoassay test was used to measure antibody levels. The percentage of the children who had antibody titres above the minimum protective level (0.01 IU/ml) was 80.0%. Only 10.6% of the children had antibody titres above the fully protective level (0.1 IU/ml). Antibody levels of children in rural areas were higher than those of children in urban areas. In children whose fathers were literate the levels were also higher than the others. Antibody level increased with the number of vaccine applications. Antibody levels were not consistent with immunization history obtained from parents. In this regard, our suggestion is that wound care management should not depend on immunization history obtained from parents if the vaccination programs are not effectively implemented. Most of the children in this study had antibody titres below the fully protective level.

Detection of antimicrobial resistance and extended-spectrum beta-lactamase production in Klebsiella pneumoniae strains from infected neonates.

The present study was designed to determine the antimicrobial resistance and extended-spectrum beta-lactamase (ESBL) activities of Klebsiella pneumoniae strains isolated from the neonatal intensive care unit of Atatürk University Hospital, Erzurum, Turkey. Antibiotic susceptibility of 40 isolates was detected by the standard disk diffusion method according to the National Committee for Clinical Laboratory Standards Guidelines. The double-disk synergy method was used to determine ESBL activity, which is associated with resistance to beta-lactam antibiotics. Twenty-four (60%) of 40 K. pneumoniae strains were found to produce ESBL. Of the antibiotics tested, meropenem was found to be the most effective (100%), and ampicillin the least effective (0%). With the increasing incidence of antimicrobial resistance, which poses a clinically significant risk to vulnerable patients, it is important that clinical microbiology laboratories have accurate and timely information concerning the strains of bacteria present to enable them to predict which antibiotics are likely to be effective in treating the infections they may cause.

Esterase activity in various Candida species.

The aim of the present study is to ascertain esterase activities of various species of Candida. A total of 125 strains isolated and identified by conventional methods were tested for esterase activity using the Tween 80 opacity test. Our results showed that 58 of 59 strains of Candida albicans, all of the Candida tropicalis strains (n = 38) and all of the Candida guilliermondii strains (n = 3) produced positive results, whereas the remaining Candida species did not. The Tween 80 opacity test is a useful method because it is simple, economical and easy to prepare and interpret.

Treatment of iatrogenic ureteral injuries during various operations for malignant conditions.

In the present study we report twenty-nine patients with iatrogenic injuries and management during various operations for malignant conditions. The patients were reviewed in order to identify and study the incidence, type of treatment administered and outcome. The study group was composed of 29 patients with 31 iatrogenic injuries between 1992 and 1999. General surgical, gynecological and urological procedures accounted for 24 (83%), 4 (14%), and 1 (3%) injuries respectively. Twenty-eight injuries were diagnosed at operation and three after an interval of 5, 17 and 45 days. Of the injuries, 51% occurred in the lower third of the ureter, 30% in the upper third and 19% in the middle third. Complete transsection, excision, ligation and partial transection accounted for 19 (61%), 9 (29%), 2 (7%), and 1 (3%) respectively. Treatment consisted of end-to-end ureteroureteral anastomosis in 18 cases; ileal interposition in 4 cases; transureteroureterostomy and ureteroneocystostomy in 2 cases; surgical repair, nephrectomy, ureterocutaneostomy and ileal loop in each of the remaining cases. Primary healing was obtained in all patients. General surgical procedures are the most common cause of iatrogenic injuries during malignant conditions. The proper identification and, when necessary, identification of the ureter at the pelvic brim, should decrease the incidence of iatrogenic ureteral injury. When identified at injury and treated immediately such injuries seldom lead to loss of renal function. We do not advocate to perform nephrectomy for any type of ureteric injury since the preservation of the kidney should be the aim of a surgeon.

Extragonadal germ cell tumors: clinicopathologic findings, staging and treatment experience in 14 patients.

Extragonadal germ cell tumors (EGCT) are a rare group of neoplasms histologically identical to testicular counterparts. Fourteen cases of primary mediastinal and retroperitoneal germ cell tumors were treated with chemotherapy and radiotherapy between 1987 and 1999 in Ankara Oncology Hospital. There were 9 (64%) complete remissions (CR),one (7%) partial remission (PR) and 2 (14%) stable diseases (SD). The remaining 2 patients were lost due to dissemination of disease. The median duration of response was 19 months. Our modified chemotherapeutic results were similar to original doses of PVB and BEP but toxicity was less. The neccesity of a uniform staging system and treatment programs are discussed.