Influence of Neuropeptide Y and Neuropeptide Y 2 Receptor Variants in Acute Coronary Syndrome

Abstract Background The neuropeptide Y (NPY) is one of the most abundant neurotransmitters in the nervous system. NPY acts as a potent stimulator of angiogenesis, inflammation, and adipogenesis, through the NPY 2 receptor (NPY2R). Changes in the NPY signaling pathway have been linked to Acute Coronary Syndrome (ACS). Objectives The purpose of this study is to determine the association between variants in the NPY and NPY2R genes, as well as the severity of acute coronary syndrome (ACS). Methods Approximately 221 ACS patients and 278 healthy controls were selected for this study. Four variants in NPY and two variants in NPY2R genes were genotyped using Taqman allelic discrimination and sequencing. The Chi-square and Fisher's exact tests were used to verify the genotype frequencies. The logistic regression analyses were used for the evaluation of the studied variables. Haplotype analysis was used to evaluate the linkage disequilibrium (LD) between the variants (p<0.05). Results An association of NPY c.20T>C variant was found with the ACS group when compared to the healthy group. In the analysis between variants and risk factors in the ACS group, NPY c.84G>A was associated with hypertension. The analysis between TIMI risk showed a significance for NPY c.20T>C between the low and intermediate/high TIMI risk groups. In the haplotype analysis, strong linkage disequilibrium (LD) was found between the variants NPY c.150G>A and NPY c.-485T>C. Conclusion The NPY c.20T>C variant appears to contribute to the development of ACS. The NPY2R c.-1116A>G variant may contribute to the early development of ACS and the NPY c.84G>A variant appears to contribute to the development of hypertension. In addition, the NPY c.20T>C is associated with a protective effect in ACS severity.

Application of Physiologically Based Pharmacokinetic Modeling of Lamotrigine Using PK-Sim in Predicting the Impact of Drug Interactions and Dosage Adjustment

Objectives To build a lamotrigine (LTG) physiologically based pharmacokinetic (PBPK) model (LTG PBPK) and compare it to the clinical data from South Asian Indian patients and use this model to understand the drug interactions of LTG and explore the optimal doses. Methods and Material The PBPK model was developed using the PK-Sim software platform and qualified with LTG plasma concentration data from an Indian study. The European population database was chosen as the patient setting in the software. Physiochemical data of LTG and enzyme kinetic data were incorporated from the literature. Dosing protocols were as per the previous study. Interaction models for drug interactions with carbamazepine and valproate were also simulated. Results Most of the model predicted concentration-time profiles of LTG at steady-state were well within the observed concentrations. The developed models were suitably qualified. The drug interaction model was used to assess the impact of induction and inhibition of the pharmacokinetic profile of LTG. Conclusions The predicted plasma concentrations of the developed PBPK models using the European population database were very similar to the data from Indian patients. The developed LTG PBPK models are applicable in predicting the impact of drug interactions and can yield appropriate LTG doses to be administered.

De novo ALX4 variant detected in child with non-syndromic craniosynostosis

Current understanding of the genetic factors contributing to the etiology of non-syndromic craniosynostosis (NSC) remains scarce. The present work investigated the presence of variants in ALX4, EFNA4, and TWIST1 genes in children with NSC to verify if variants within these genes may contribute to the occurrence of these abnormal phenotypes. A total of 101 children (aged 45.07±40.94 months) with NSC participated in this cross-sectional study. Parents and siblings of the probands were invited to participate. Medical and family history of craniosynostosis were documented. Biological samples were collected to obtain genomic DNA. Coding exons of human TWIST1, ALX4, and EFNA4 genes were amplified by polymerase chain reaction and Sanger sequenced. Five missense variants were identified in ALX4 in children with bilateral coronal, sagittal, and metopic synostosis. A de novo ALX4 variant, c.799G>A: p.Ala267Thr, was identified in a proband with sagittal synostosis. Three missense variants were identified in the EFNA4 gene in children with metopic and sagittal synostosis. A TWIST1 variant occurred in a child with unilateral coronal synostosis. Variants were predicted to be among the 0.1% (TWIST1, c.380C>A: p. Ala127Glu) and 1% (ALX4, c.769C>T: p.Arg257Cys, c.799G>A: p.Ala267Thr, c.929G>A: p.Gly310Asp; EFNA4, c.178C>T: p.His60Tyr, C.283A>G: p.Lys95Glu, c.349C>A: Pro117Thr) most deleterious variants in the human genome. With the exception of ALX4, c.799G>A: p.Ala267Thr, all other variants were present in at least one non-affected family member, suggesting incomplete penetrance. Thus, these variants may contribute to the development of craniosynostosis, and should not be discarded as potential candidate genes in the diagnosis of this condition.

Patient preferences and expectation for feedback on adverse drug reaction reports submitted in Ghana

Background: Personalized feedback received for spontaneous adverse drug reaction (ADR) reports serves as motivation for future reporting and the effectiveness of the feedback is dependent on the medium used in delivering the information. Objective: Explore expectation for feedback from patients on ADR reports submitted to the National Pharmacovigilance Centre (NPvC) in Ghana and the preferred medium for receiving the feedback information.Methods: Cross-sectional study using structured questionnaire administered through face-to-face interview from August to September 2016 to patients selected by convenience sampling. Pearson chi-square (Χ2) or Fisher's exact test was used to determine associations between background variables such as age, gender and level of education. Results: The response rate was 86.7% (n=442). Of the participants interviewed, 96.5% expected to receive feedback for ADR reports submitted. Age and level of education were the two variables significantly associated with patients' expectation for feedback. The preferred medium for receiving feedback in decreasing order of preference were, telephone call (60.4%), mobile phone short messaging services (23.0%), email (8.3%), face-to-face meeting (3.4%), personalized letter (3.4%) and publication in a newsletter (1.4%). Conclusion: Patients' expectation for receiving feedback for ADR reports submitted to the NPvC is in line with modern trends in communication. NPvC should explore these alternatives for providing feedback to patients. Thisstudy is limited to what patients' expectations and preferences were for receiving feedback on ADR reports submitted, additional study to further explore the type of information patients expect to be contained in the feedback will be useful to National Pharmacovigilance Centres

Stem Cells in Deciduous Teeth ­ Their Potential use in Medicine

The potency and quality of adult stem cells in our body is reversely proportional to our age. When stem cells were discovered in deciduous teeth, it has drawn much attention to the dental and medical fields. Because these cells are normally from children shedding teeth around ages 6-12, they are relatively more immature stem cells. The isolated stem cells from the pulp of deciduous teeth were named SHED (stem cells from exfoliated deciduous teeth) [1]. As other dental stem cells, SHED are a type of typical mesenchymal stromal/stem cells (MSCs) expressing CD146, CD105, CD73, CD29 and CD44; as well as expressing embryonic stem (ES) cell markers OCT4, NANOG, stage-specific embryonic antigens (SSEA-3, SSEA-4) and tumor recognition antigens (TRA-1-60 and TRA-1-81) [2].

Access and Intensity of Mechanization: Empirical Evidence of Rice Farmers in Southern Ghana

ABSTRACT The medium term development plan of Ghana proposed modernization of agriculture to lead the way in transforming the economy. Providing irrigation infrastructure and enhancing farmer access to farm machinery were major interventions proposed. In line with this, the government has been investing in irrigation infrastructure as well as importing farm machinery under various programmes in recent years. This study analyzed access and intensity of mechanization by rice farmers in southern Ghana. The Shai-Osudoku and Ketu North Districts were purposively selected and a total of 360 farmers were randomly sampled from 16 rice growing communities. In general, the results of the descriptive statistics revealed that about 74 % of farmers were still cultivating rice with considerably low level of mechanization. The double hurdle model was employed to estimate the determinants of access to mechanization and the intensity of mechanization. The empirical results of tier one of the double huddle model revealed that size of land, access to credit, availability of farm machinery, expenditure on labour, agrochemical expenditure, the square of age, and gender positively influenced access to mechanization. Seed expenditure, age and district locations negatively influenced access to mechanization. The empirical results of the tier two of the double hurdle model revealed that distance from farm to nearest mechanization centre, rice income, non-farm income and experience were significant variables that positively influenced intensity of mechanization. Land ownership and household size negatively influenced intensity of mechanization. These results have implications for capacity building and government support for rice farmers in southern Ghana.

Prediction of lymph node metastases by preoperative nuclear morphometry in oral squamous cell carcinoma: A comparative image analysis study.

Context: Prediction of metastases of oral squamous cell carcinoma (OSCC) using incisional biopsy. Aims: To assess the efficacy of nuclear morphometry in predicting the nodal metastases of OSCC and to compare manual and computer-based image analyses. Materials and Methods: Sixteen cases of moderately differentiated squamous cell carcinoma (8 with metastasized lymph nodes and 8 node-negative cases) were examined using manual and computer-based image analyses. Nuclear area, perimeter, circular rate, larger to shorter axis ratio, and coefficient of variance of nuclear area (NACV) were calculated from 100 nuclei of the processed incisional biopsy specimen. Statistical Analysis: The parameters were compared between the node positive and negative cases using Student's t test and with the level of lymph node involved using ANOVA test and Bonferroni's post hoc assessment. Manual and computer-based image analyses were compared by Spearman's correlation. Results: A significant variation between the node positive and negative groups was observed with respect to circular rate (P = 0.031) and NACV (P = 0.036). The nuclear area (P = 0.009), perimeter (P = 0.0001), circularity (P = 0.045), and larger to shorter diameter ratio (LS ratio) (P =0.02) were significantly different in the levels of the nodes involved. There was good a correlation between manual and computer-based analyses (Spearman's rho, 0.616-0.824) in nuclear size parameters and the circular rate had a negative correlation (-0.118, P = 0.664). Nuclear circularity was better assessed by computer-based analysis. Conclusion: Preoperative morphometric assessment of the nuclear features may detect early cellular changes and thus, are useful in predicting nodal metastases in OSCC.

Nasal carriage of staphylococcus aureus and antibiotic susceptibility pattern among children in Freetown; Sierra Leone

Nasal carriage of Staphylococcus aureus has been demonstrated to be a major risk factor for invasive S. aureus infections in various population including children. The extent of S. aureus carriage in Sierra Leonean children is largely unknown. To determine the prevalence and pattern of antibiotic susceptibility of nasal S. aureus among children in Freetown; Sierra Leone; samples were collected from anterior nares of children less than two years at the Ola During Children's Hospital between October 2008 and April 2009. Of the 116 children screened during the study period; S. aureus isolates were found in the nasal specimens of 40 (34.5) of the children. Antimicrobial susceptibility testing to norfloxacin; gentamycin; erythromycin; trimethoprim-sulfamethazole; doxycycline; tetracycline and amoxycillin-clavulanic acid were observed to be 95; 35; 30; 20; 15; 7.5 and 2.5respectively. All the isolates were susceptible to oxacillin and resistant to chloramphenicol; penicillin G; amoxycillin and ampiclox. Regular monitoring of antimicrobial susceptibility pattern may be useful

Skin lesions in renal transplant recipients: A single center analysis.

Background: The chronic use of immunosuppressants in renal transplant recipients (RTRs) predisposes them to a variety of skin manifestations. Studies on skin lesions in RTRs from India have been limited. Aim: To study the prevalence and clinical spectrum of skin diseases in RTR in patients attending the Nephrology clinic of a tertiary care hospital in South India. Methods: Between October 2002 and June 2003, 365 RTRs were evaluated for skin lesions, including 280 examined after renal transplant (group A) and 85 examined once before and then monthly after transplant for a period of 6 months (group B). Results: A total of 1163 skin lesions were examined in 346 RTRs (94.7%) including lesions of aesthetic interest (LAI) [62.3%] followed by infections [27.3%]. All LAI were drug-related manifestations, making it the most common skin lesion, while fungal (58.7%) and viral (29.3%) infections constituted majority of lesions caused by infection. Lesions related to neoplasms were relatively uncommon (2.1%) and all lesions were benign. Miscellaneous lesions constituted 8.3% of skin lesions, which included vaccine-induced necrobiotic granulomas at the site of Hepatitis B vaccination and acquired perforating dermatoses. Conclusion: Skin lesions among RTRs from India consist predominantly of drug-related LAI and infections and are different from the West in view of the paucity of neoplastic lesions.

A rare presentation of oral pemphigus vulgaris as multiple pustules.

Pemphigus vulgaris is an autoimmune blistering disease affecting the mucous membrane and skin. Ulcers, vesicles, bulla, erosions are the common manifestations of the disease. It is uncommon to find multiple pustular lesions in the oral cavity. Here, we report the first case of multiple pustules involving the lateral borders of tongue, buccal mucosa, hard palate, soft palate, vestibule and the gingiva of a 53 year old male. Histopathologic and Immunofluoroscence study was suggestive of pemphigus vulgaris. The condition improved with systemic corticosteroid along with adjuvant therapy. Key words: pemphigus vulgaris, multiple pustules, immunofluorescence, corticosteroids.

Infections with atypical mycobacteria in renal transplant recipients.

Infections due to atypical mycobacteria are infrequent in renal transplant recipients but they cause serious morbidity. These pathogens are common in patients with acquired immune deficiency syndrome (AIDS). We report four proven cases of infections caused with atypical mycobacteriae from 1997 to 2003, by different organisms namely, M. chelonei, M.fortuitum, M. abcessus and M. terrae in renal transplant recipients. Infection with M. terrae documented here is the first occurrence in a renal transplant patient. Histopathological examination of aspirates or biopsy specimens from involved areas and staining and culture for mycobacteriae are essential for diagnosis. Treatment involves antimycobacterial therapy, reduction in immunosuppression and surgery, if indicated. Atypical mycobacterial infections, though currently uncommon, are significant and could prove to be an emerging pathogen in renal transplant recipients in the context of the AIDS epidemic in India.

Prevalence of proteinuria in rural adult population in Tamil Nadu.

BACKGROUND & OBJECTIVES: Presence of proteinuria is considered as an early marker of an increased risk of progressive kidney disease. Angiotensin converting enzyme (ACE) inhibitors (ACEi) and angiotensin II receptor blockers (ARB) treatment to persons with proteinuria and chronic kidney disease has been shown to decrease the progression to endstage renal disease. As the exact prevalence of proteinuria is not known in the general population, we undertook this study to estimate the same in a rural adult population in Vellore district, Tamil Nadu. METHODS: A convenient sample of 5,043 adults was included. All individuals were tested for albuminuria by albumin dipstick examination in an untimed urine sample. Individuals who tested positive for albuminuria underwent a second dipstick examination after a gap of one week. Individuals with persistent albuminuria on the second dipstick examination underwent further evaluation which included medical history, physical examination, 24 h urine protein estimation, total serum protein and albumin estimation. Ultrasound of the abdomen was done in patients with renal failure and renal biopsy was performed in selected patients. RESULTS: Of the total 5,043 individuals screened, 63.1 per cent were females. Mean age of the study population was 50.94 +/- 11.2 yr. First dipstick test identified 594 individuals positive for albuminuria. Repeat dipstick could be done in only 576, of whom 212 showed persistent albuminuria. Significant proteinuria was detected in 24 individuals of the 208 who had 24 h urine protein measured. Of these 24 patients, 3 were found to have chronic renal failure, 12 were presumed to have diabetic nephropathy clinically, one each had focal segmental glomerulosclerosis and biopsy proven diabetic nephropathy, and 7 patients had proteinuria of unknown aetiology. INTERPRETATION & CONCLUSION: The prevalence of proteinuria in this adult rural population was 0.47 per cent (0.30-0.67%). The detection and treatment of chronic kidney disease in 24 individuals is bound to reduce the rate of decline of renal functions. Screening programme for proteinuria in different parts of country may be an effective measure to bring a decline in rate of progression of chronic kidney disease in general population.

Familial chylomicronemia syndrome.

Familial chylomicronemia syndrome is a group of rare genetic disorders characterized by deficient activity of an enzyme lipoprotein lipase or apo-protein C-II deficiency. Incidence is 1 out of 1,000,000. Alternative names to this syndrome are Type I hyper lipoproteinemia and familial lipoprotein lipase deficiency.

Granulocyte macrophage colony stimulating factor augmented hepatitis B vaccine protocol for rapid seroprotection in voluntary kidney donors.

BACKGROUND & OBJECTIVES: Conventional hepatitis B vaccine protocols do not provide rapid seroprotection against hepatitis B. This randomized controlled trial was carried out to investigate the efficacy of granulocyte macrophage-colony stimulating factor (GM-CSF) augmented double-dose vaccine protocol in voluntary kidney donors prior to donor nephrectomy. METHODS: A total of 54 kidney donors, who had no history of hepatitis B infection, hepatitis B vaccination and tested negative for anti-HBs and anti-HBc antibodies were randomly allocated to the control or test groups. GM-CSF (300 microg) was administered subcutaneously on day 0, followed by 40 microg of recombinant hepatitis B vaccine intramuscularly on the same deltoid on day 1. The control group received only 40 microg of intramuscular hepatitis B vaccine. Anti-HBs titres were measured at the end of 4 wk. RESULTS: Of the 54 donors studied, there was a significant (P<0.003) seroconversion in the GM-CSF group (82%) compared to the control group (37%), after a single immunization with double-dose recombinant hepatitis B vaccine by 4 wk. Minor side effects such as fever in four patients and myalgia in three were noticed. INTERPRETATION & CONCLUSION: GM-CSF augmented double-dose hepatitis B vaccine could be used in unvaccinated patients when a rapid response is desired.

Exclusive carbon dioxide-guided renal artery stenting in a case of Takayasu's arteritis with a solitary functioning kidney.

We report the case of a 28-year-old female with type II Takayasu's arteritis affecting her single functioning kidney. Impaired renal function precluded the use of conventional contrast media. We used carbon dioxide-guided renal angioplasty to successfully treat the patient.

Management of phacolytic glaucoma: experience of 135 cases.

We retrospectively analyzed 135 eyes with phacolytic glaucoma. A trabeculectomy was added to standard cataract surgery if symptoms endured for more than seven days, or if preoperative control of intraocular pressure (IOP) with maximal medical treatment was inadequate. In the early postoperative period, IOP was significantly lower in the combined surgery group (89 eyes) compared to the cataract surgery group (46 eyes) (p < 0.001). At 6 months there was no difference in IOP or visual acuity between the two groups. There were no serious complications related to trabeculectomy. It is reasonable to conclude that in eyes with a long duration of phacolytic glaucoma, addition of a trabeculectomy to cataract surgery is safe, prevents postoperative rise in intraocular pressure and decreases the need for systemic hypotensive medications. A randomized trial is on to further address this question.