Bioinformatics of thymidine metabolism in Trypanosoma evansi: exploring nucleoside deoxyribosyltransferase (NDRT) as a drug target

@#Trypanosoma evansi, the causative agent of surra or camel trypanosomiasis, is characterized by the widest geographic distribution and host range among the known trypanosomes. Its zoonotic importance and increasing evidence of drug resistance necessitate the discovery of new drug targets. The drug discovery process entails finding an exploitable difference between the host and the parasite. In this study, the thymidine metabolic pathways in camel and T. evansi were compared by analyzing their metabolic maps, protein sequences, domain and motif contents, phylogenetic relationships, and 3D structure models. The two organisms were revealed to recycle thymidine differently: performed by thymidine phosphorylase in camels (Camelus genus), this role in T. evansi was associated with nucleoside deoxyribosyltransferase (NDRT), a unique trypanosomal enzyme absent in camels. Thymidine in T. evansi seems to be governed by thymine through NDRT, whereas in camels, thymidine can be produced from thymidylate via 5'-nucleotidase. As a result, NDRT may be a promising drug target against T. evansi.

Behavioral and emotional effects of repeated general anesthesia in young children

Preclinical and clinical data suggest the possibility of neurotoxicity following exposure of young children to general anesthetics with subsequent behavioral disturbances. The aim of the study was to determine the overall effect of repeated general anesthesia on behavior and emotions of young children aged 1½-5 years old, compared to healthy children. Thirty-five children underwent repeated anesthesia and surgery were matched with the same number of healthy children who attended vaccination clinic, as a control group. Both groups were administered the child behavior checklist [CBCL] 1½-5 years and Diagnostic and Statistical Manual of Mental Disorders [DSM] oriented scale. Behavior data were collected through a semi-structured questionnaire. The CBCL score revealed that children with repeated anesthesia were at risk to become anxious or depressed [relative risk [RR]; 95% confidence interval [CI] = 11 [1.5-80.7]], to have sleep [RR; 95% CI = 4.5 [1.1-19.4]], and attention problems [RR; 95% CI = 8 [1.1-60.6]]. There was no difference in the risk between the two groups regarding emotionally reactive, somatic complaints, withdrawn problems, aggressive behavior, internalizing or externalizing problems. On DSM scale, children with repeated anesthesia were at risk to develop anxiety problems [RR; 95% CI = 3.7 [1.1-12.0]], and attention deficit/hyperactivity problems [RR; 95% CI = 3 [1.1-8.4]]. There was no difference in the risk between the two groups regarding affective, pervasive developmental and oppositional defiant problems. Young children who undergone repeated surgical procedures under general anesthesia were at risk for subsequent behavioral and emotional disturbances. Proper perioperative pain management, social support, and avoidance of unpleasant surgical experiences could minimize these untoward consequences

[Characterisation of nicotine and Cancer-Enhancing Anions in the common smokeless tobacco Afzal in Oman]

Objectives: Afzal is a common smokeless tobacco product [STP] available illegally in Oman. This study aimed to assess pH and moisture levels and determine cancer-enhancing factors in a randomly selected sample of Afzal

Methods: This study was carried out at the Sultan Qaboos University in Muscat, Oman, between April and December 2013. A package of Afzal was purchased from a single provider and divided into samples. The pH and moisture content of the samples were measured according to the protocols of the Centers for Disease Control and Prevention. Gas chromatography-mass spectrometry was used to analyse nicotine levels and ionexchange chromatography [IC] was used to determine concentrations of nitrate, nitrite, chloride, fluoride, bromide, sulphate and phosphate anions

Results: The samples had an alkaline pH of 10.46 with high levels of total [48,770.00 micro per g of STP [microg/g]] and unionised [48,590.00 microg/g] nicotine. The concentration of nitrate [8,792.20 microg/g] was alarmingly high. The chloride concentration [33,170.80 microg/g] showed a surge on IC chromatography. The moisture content percentage was 52.00%

Conclusion: The moisture content percentage and chloride concentration of Afzal was consistent with those of other STPs. In contrast, nitrite, sulphate and phosphate concentrations were below reported levels of other STPs. All anion concentrations were below the maximum daily limit set by international health organisations. However, the high concentrations of nitrite, nitrate and nicotine and the elevated alkaline pH observed in the analysed Afzal samples suggest that STP users will face health risks as a result of their use

Associations between spontaneous preterm birth and maternal-newborn ABO blood phenotype pairs

To study whether spontaneous preterm birth [SPB] is associated with maternal-newborn ABO blood phenotype pairs. We conducted a retrospective case-control study in the Department of Pediatrics, King Abdulaziz Hospital, Al-Ahsa, Kingdom of Saudi Arabia. A total of 631 live singleton SPBs [<37 weeks] between August 2005 and May 2011 formed the case group. A total of 2,204 live singleton term births [>/= 37 weeks] between May 2008 and April 2009 formed the control group. We extracted data on the mothers and their newborns from our neonatal electronic database and delivery room log book. We extracted ABO blood phenotypes using Cerner's Lab Information Software. We used a Chi square test to study the association between SPB and maternal-newborn ABO pairs. We used a combination of maternal-newborn A-A, B-B, AB-AB, and O-O pairs as the reference group. We used a binary logistic regression analysis to adjust for 6 established risk factors for SPB. Spontaneous preterm birth was associated with only maternal-newborn pairs B-A [odds ratio: 2.67, 95% confidence interval: 1.35-5.24, p=0.003] and AB-B [odds ratio: 1.97, 95% confidence interval: 1.04-3.74, p=0.04]. Both associations remained significant in the regression analysis. Spontaneous preterm birth is associated with maternal-newborn B-A and AB-B pairs. This finding requires further confirmatory and exploratory study as it could reduce SPBs.

Hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient male newborns in Al-Ahsa, Saudi Arabia

To study the clinical and laboratory characteristics of hyperbilirubinemia in glucose-6-phosphate dehydrogenase [G6PD]-deficient male newborns from Al-Ahsa area [Ahsais]. The medical records of inborn male infants at King Abdulaziz Hospital [KAH] in Al-Ahsa area, Kingdom of Saudi Arabia from May 2008 through April 2009 were reviewed. Inclusion criteria were healthy non-polycythemic G6PD-deficient Ahsa males born at >/= 37 weeks gestation, weighing >/= 2.5 kg, with no other cause of hyperbilirubinemia, and were sampled for a total serum bilirubin [TSB] within the first 48 hours of life. Hyperbilirubinemics were compared with non-hyperbilirubinemic newborns. Among the 93 G6PD-deficient newborns that met the inclusion criteria, 67 were hyperbilirubinemic and required phototherapy, and 13 of them required rephototherapy. Phototherapy was started at 11 +/- 4 [mean +/- SD] hours of life, and for a total duration of 42 +/- 28 hours. Hyperbilirubinemics had statistically significant higher levels of both hematocrit [53 +/- 6 versus 49 +/- 8%, p=0.02] and hemoglobin [176 +/- 18 versus 166 +/- 21 g/ L, p=0.04], and lower reticulocyte percentage [4.3 +/- 0.7 versus 5.2 +/- 1.0%, p=0.02], when compared to non-hyperbilirubinemic newborns. Hyperbilirubinemia in G6PD-deficient Ahsai male newborns was characterized by higher levels of both hematocrit and hemoglobin levels, and lower reticulocyte percentage compared to their non-hyperbilirubinemic counterpart. This hyperbilirubinemia required early phototherapy and re-phototherapy. Appropriate follow up should be made available to those high-risk newborns. Further research is needed to understand the exact mechanism of hyperbilirubinemia in G6PD-deficient newborns

Potential adverse effects of antenatal ultrasonography

Ultrasonography is the imaging modality of choice for pregnancy evaluation due to its relatively low cost, real-time capability, and operator comfort. Majority of practitioners feel that antenatal ultrasonography is a safe study for infants, while other practitioners are not so convinced of ultrasongraphic safety and feel that judicious use is advised

Cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is a disorder that affects mostly those bones which derived from endochrondal and intramembranous ossification, such as the cranium and the clavicles. CCD is present at a frequency of one in one million individuals. Over 500 cases have been reported. A 13 years old boy reported in the Paediatric Endocrinology outpatient department, Bangladesh Institute of Research and Rehabilitation on Diabetes, Endocrine and Metabolic Disorders (BIRDEM) on 6th April 2006 with complaints of not growing according to his age, a wide gap over the head since birth and delayed shedding of primary teeth and also eruption of secondary teeth. The boy had elongated facies with midfacial hypoplasia, depressed nasal bridge with hypertelorism. His anterior fontanelle was open about 3/1.5 cm. He had short clavicle and his shoulders could be easily apposed. Radiological findings showed anterior fontanellle and sutures were open and widened, all decidual teeth were intact and all secondary teeth were impacted beneath the primary teeth and hypoplastic clavicle. He was diagnosed as a case of Cleidocranial Dysplasia on the basis of history, clinical examination and investigation.

Trends and determinants among cardiac disabled workers in Alexandria

The present study was designed to investigate the trend and determinant factors among cardiac disabled workers presented in the years 2003-2005 at Health Insurance Committee for disability rating in Alexandria and to compare the currently used system with others. A retrospective study was conducted to review complete records for those below the age 65 years. The available data were coded to include age, gender, job title, disabling symptoms, presence or absence of abnormal findings in resting electrocardiogram and chest X-ray. Extra-investigations were considered by the committee in some cases including echocardiography, cardiac stress test and coronary angiography. Therapeutic interventions were coded and etiological diagnosis was classified into ischemic heart disease [IHD], rheumatic heart disease [RHD], hypertension [HT] and cardiomyopathies [CM]. The functional diagnosis was reported as presence or absence of heart failure and disability was rated as partial or total. Results revealed that rates of disabling dyspnoea, CM and heart failure were significantly increasing from year to year [p=0.038, 0.039 and 0.023 respectively]. The most common etiological diagnosis for the presented cases was IHD with high rates ranging from 69.7% to 73.6% across the 3 years. Logistic regression with total disability as the dependent variable showed that heart failure and additional information by echocardiography were the independent determinants [p= 0.020 and 0.004 respectively]. Simplified comparison between current cardiac disability rating system and American medical Association impairment classification was given. The present disability rating system lack standardization and quantification. It is recommended to integrate the metabolic equivalent [METs] measurement with the current system. Also to emphasize cardiovascular preventive programs to control cardiac disability

Gene expression profiling in women with breast cancer in a Saudi population

To generate consensus gene expression profiles of invasive breast tumors from a small cohort of Saudi females, and to explore the possibility that they may be broadly conserved between Caucasian and Middle Eastern populations. This study was performed at King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia, from January 2005 to January 2007. Gene expression profiles were generated from 38 invasive breast tumors, and 8 tumor adjacent tissues [TATs] using BD Atlas cDNA expression arrays containing 1176 genes. Results were confirmed by reverse transcriptase polymerase chain reaction, and analyzed by 2-dimensional unsupervised hierarchical clustering. The analysis identified 48 differentially expressed genes in tumors from which 25 are already reported by various western studies. Forty-three of these genes were also differentially expressed in TATs. The same data set has been able to distinguish between tumors and the TATs, interestingly by using only 4 of the differentially expressed genes. Moreover, we were able to group the patients according to prognosis to an extent by hierarchical clustering. Our results indicate that expression profiles between Saudi females with breast cancer and the Caucasian population are conserved to some extent, and can be used to classify patients according to prognostic groups. We also suggest 3 differentially-expressed genes [IGHG3, CDK6, and RPS9] in tumors may have a novel role in breast cancer. In addition, the role of TATs is much more essential in breast cancer, and needs to be explored thoroughly

Serum Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) Levels in Different Grades of Protein Energy Malnutrition.

The present study was designed to analyze serum AST, ALT levels in different grades of protein energy malnutrition to facilitate early diagnosis, management and rehabilitation of PEM. The serum AST and ALT levels of 50 children of aged 5months to 5 years of both sexes were studied. Among them, 30 children suffering from protein energy malnutrition of 3 different grades were selected for experimental group. Age and sex matched 20 apparently healthy children with no systemic disorder and with weight/height ratio greater than 80% were included in control group. Serum AST and ALT levels were measured by kinetic ultraviolet method according to International Federation of Clinical Chemistry.. Data were analyzed statistically by un paired student “t” test. Mean Serum AST and ALT levels of different grades of protein energy malnutrition were significantly higher(p<0.001) than that of control. Values of mean serum AST and ALT levels were highest in grade-I PEM and it were significantly higher(p<0.001) than both grade-II and grade-III. Again mean serum AST and ALT levels were significantly higher (p<0.001) in grade-II PEM than that of grade-III PEM. The elevated levels of serum AST and ALT is due to tissue break down and hepatobiliary disorder. The results of this study indicate that serum ALT and AST levels are increased in PEM which varies according to its severity.

effect of hysterectomy on psychiatric morbidity [anxiety and depression]

To evaluate the psychiatric morbidity [anxiety and depression] in women underwent an abdominal and vaginal hysterectomy of a benign indication. This is a prospective observational study which was done in the Obstetric and Gynecology and Neuropsychiatry Departments, Sohag University Hospital. One hundred and two women were scheduled for undergoing hysterectomy after fulfilling the inclusion criteria. All women underwent a thorough history taking, clinical examination and complete psychiatric history. General health questionnaire [GHQ-28] was used to assess women with psychiatric co-morbidity before and after the operation. All women with psychiatric co-morbidity were re-evaluated by Beck depression inventory [BDI] and Hamilton anxiety scale [HAMA] before and after hysterectomy. On screening for psychiatric co-morbidity using the GHQ-28 for the 96 women who completed the follow up protocol of the study 35 [36.46%] scored >/= 4 [Group I] with psychiatric co-morbidity, and 61 [63.54%] scored <4 [Group II] without psychiatric co-morbidity. GHQ-28 was reapplied to all women in group II [post-operatively] where 48 [78.69%] scored >/= 4 [group IIa] and 13 [21.31%] scored <4 [group IIb. Severe anxiety and depressive symptomes were the most common presentation after the operation and represented 8 [40%] and 8 [53.3%], of patients of group I, respectively. In patient, of group II [without psychiatric morbidity] after hysterectomy, depressive and anxiety symptoms was the most common presentation in nulliparous women and was found in 7 [63.64%] and 3 [27.27%], respectively. However, the least depressive and anxiety symptoms was observed in women with parity >/= 5 and was found in 12 [38.7%] and 9 [29.03%], respectively. It is not worthy that the majority of women free from psychiatric co-morbidity was observed in women with parity >/= 5 and represented 10 [32.5%] of patients. It was clear that there was a definite significant relation between hysterectomized women and psychiatric morbidity of a depressive and anxiety nature. So we recommend that before hysterectomy in benign conditions, gynecologists should exhaust great effort of using the available recent less invasive modalities of treatment as first option

Effect of metformin and antioxidant agents on oxidative stress status and follicular maturation in women with polcystic ovary syndrome

In this study, forty-two Iraqi Arab Women with PCOS were involved and they were classified into three groups according to type of treatment:1] Group I: fourteen patients who administered metformin [500mg t.i.d]. 2] Group II: fourteen patients who administered combination of metformin [500mg t.i.d] with vitamin C [250mg t.i.d] 3] Group III: fourteen patients who administered combination of metformin [500mg t.i.d] with vitamin E [200mg t.i.d].All groups were treated for three months. The present study includes the measurement of serum malondialdehyde, Vitamin E and its metabolite [tocopheronic acid] play an important role in alleviation of oxidative stress [MDA] and may potentiate the metformin activity in maturation of follicles

Gene expression profiles of the flbroblasts from breast tumors and normal tissue compared with the tumor expression profiles

The study was designed to examine whether the gene expression profiles of fibroblast cell lines, established from the tumor and the normal tissue from the same breast, exhibit any similarities with the profiles of the original tissues. Fibroblast cell lines were established from invasive ductal carcinoma [IDC] and ductal carcinoma in situ [DCIS] of the breast and the adjacent normal tissues. Isolated total RNA from the cell lines and tissues were used to prepare labeled cDNA which was hybridized to Becton Dickinson Atlas TM microarrays for obtaining profiles of expressed genes. The profiles of tumors and cell lines were compared. This study was carried out at King Faisal specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia, during 2004 and 2005. Alterations of expression of most of the genes in the tissues were not detectable in the cell lines. The expression of a lower number of genes was altered in DCIS compared with that in IDC tumors. Although the fibroblasts discharge important functions, their gene expression profiles do not represent the breast tissue to the extent that any prognostic decisions could be made

Tubularized incised-plate urethroplasty for secondary hypospadias repair

Reoperation for failed hypospadias has been considered to be seriously bothersome because abundant penile skin does not tend to remain for urethroplasty or for penile shaft skin coverage. In this study we evaluated the results of tubularized incised plate [TIP] urethroplasty [Snodgrass technique] in a series of secondary hypospadias repair in children. From March 2003 to September 2004, a total of 28 patients with hypospadias in whom repair had failed, underwent a re-operative TIP urethroplasty. The patients age ranged from 2 to 14 years. The number of prior repairs ranged from one to five repairs. Before this treatment the meatus was at the distal shaft in 16 cases, mid shaft in 9 and proximal shaft in 3. Preoperatively, the associated complications were fistulas in 7 patients and residual chordee in 4. In 5 cases the fistulas were incorporated into the hypospadiac openings and treated as a longer defect. The urethral plates were subjectively, surgically altered or unaltered in 8 and 20 respectively. In 17 patients [group A] the previous repair[s] did not involve dissection of the urethral plate [unaltered] nor was there a fistula. The remaining 11 patients were classified as group B. The neourethra was then reconstructed as the Snodgrass technique. The mean follow up period was 10 months. There were 11 complications in 7 patients [25%], including a small fistula in 4 [14%] and meatal stenosis in 7 [25%]. All complications occurred in group B except for 2 cases of meatal stenosis which occurred in group A and treated with simple dilatation. We conclude that TIP urethroplasty is a viable option for the treatment of previously failed hypospadias repair. It was highly effective in patients with a surgically unaltered urethral plate

Preliminary report on treatment of perilunar fracture dislocation

Perilunate dislocation and fracture dislocations are uncommon injuries of the wrist. The aim of the present study was to present an experience in treating such rare injuries. Nine patients were treated within three years [two patients were lost in follow up and the remaining seven patients had an average follow up of 25.8 months]. There were two perilunate dislocations and five fracture dislocations. The fracture dislocation group was treated within hours of injury. The two perilunate dislocations were delayed for 7 and 17 days post injury; these two cases had open reduction and percutaneous fixation. The fracture dislocation group had an immediate closed reduction and percutaneous fixation of the fracture and intercarpal joints. One case had open reduction and Herbert screw fixation of the scaphoid fracture with percutaneous fixation of the intercarpal joints. A functional scoring system and X-ray findings were used for the follow up evaluation. Three patients had excellent results, three patients had good results and one had fair result

VOCs-enrichment factor as an indicator of IAQ and health problems in economic residences in Alexandria

Indoor air quality of 5 blocks in Alexandria was investigated. VOCs-enrichment factor [VEF], that is potentially useful in lAQ investigations was evaluated in this study. Concentrations of VOCs and CO 2 were determined for 26 units and VEF was calculated. 100 housewives were selected randomly for the study [20 from each block]. For each subject, an interview, general and systemic examination, pulmonary function tests, and radiological examination were carried out. The most frequent complaint among the study population was the nonspecific complaints [51%] followed by respiratory system complaints [34%], while 28% of the studied sample reported mental complaints. There have been many studies in residences, but few include both VOCs and CO 2 concentrations. Although VOCs concentrations vary over a large range of concentrations for indoor [0.150-2.989 mg/m 3] and for outdoor [0.123-2.975 mg/m 3], the presence of elevated VOCs indicates strong contaminating source in the building. Outdoor VOCs concentration can be quite variable reflecting vehicular, commercial, and industrial emissions. CO 2 is a crude indicator of ventilation efficiency. 65% of units had VEF of about 1 indicating that bioeffluent emissions prevail, 23% of units had VEF>5 which indicates existence of strong abiotic VOCs sources, and 12% of units had VEF < 0.3 which indicates existence of large combustion source of CO 2 Adverse health responses potentially caused by VOCs in non-industrial indoor environment are irritant, systemic, and toxic effect. In addition, symptoms such as headache, fatigue, and mental confusion are indicators of the presence of combustion products such as CO 2. The VEF is applicable to residences and the present study suggests that people suspecting a connection between their health impairment and housing conditions should be taken seriously

Intralesional verapamil injection in treatment of Peyronie's disease. Preliminary results

Objective To evaluate the efficacy of intra-lesional verapamil injection in the treatment of Peyronie's disease. Patients and Methods Twenty-six patients with Peyronie's disease were divided into two groups: the verapamil treatment group (study group) including 13 patients and the saline group (control group) including another 13 patients. The patients' age ranged from 35 to 58 years with a mean age of 43.75 years. The patients in the study group were subjected to a weekly injection of 10 mg verapamil hydrochloride (5 mg / 2 ml) into the plaque for the duration of six weeks. At the same time; the patients in the control group received a weekly injection of normal saline into the plaque; also for the duration of six weeks. The patients' response to the injections was evaluated subjectively with respect to pain and sexual dysfunction and objectively with respect to the plaque volume and the degree of curvature. Results Following therapy; pain was improved in 8 of 9 patients (88.9) of the patients in the verapamil group; while in the control group it was stationary in 6 of 8 patients (75) and had progressed in 2 of 8 patients (25). Curvature was improved in 5 of 10 patients (50) and remained unchanged in 5 of 10 patients (50) of the study group; while no improvement could be recorded in any of the patients of the control group. Three of five patients (60) of

Management of renal trauma : assiut experience

Objective To conform a rational approach for diagnosis and treatment of renal injuries with either conservative or interventional treatment. Patients and Methods The study included 36 male and 6 female patients (total 42) with renal trauma. The patients' age ranged from 6 to 65 years. Thirty-one patients (73.8) presented with blunt renal trauma; while eleven patients (26.2) presented with penetrating renal trauma. Haematuria was the commonest presenting symptom accounting for 98. All patients were thoroughly evaluated clinically and by abdo-minal ultrasonography; while excretory urography and abdominal computerized tomography were required in some patients only. Results Conservative treatment was successful in 10 patients with minor blunt trauma; while immediate exploration was done for 26 patients and late exploration was required in 6 patients. Conclusion For renal salvage; the traumatized kidney is to be explored in all cases of penetrating and major blunt renal trauma

Treatment of hepatocellular carcinoma associated with cirrhosis by ultrasonograhic guided percutaneous ethanol injection

This study aimed to evaluate the short-term response to ultrasonographic guided percutaneous ethanol injection [PEI] for hepatocellular carcinoma [HCC] in cirrhotic patients. The study included 20 cirrhotic patients with HHC. Cases with severe liver impairment [Child's class C], severe bleeding tendency, impaired prothrombin concentration, thrombocytopenia, big tumors [more than 5 cm] or more than one tumor were excluded from the study. The patients were treated with percutaneous injection of ethanol 95% under guidance with ultrasound. The total amount of injected ethanol per session was between 5-20 ml. One to nine administrations were performed for each lesion according to its size. No serious complications occurred during or after treatment. The patients were followed up for 9-12 months. All lesions had post treatment sonographic structured changes of fibronecrotic echopattern. All patients were followed up by aspiration cytology at the end of treatment and at three and six months and yielded negative results for malignancy in all cases, except one who responded adequately to re-injection, with a significant reduction in the tumor size. Alpha fetoprotein level dropped significantly. No biochemical changes or untoward clinical sequelae were detected