Pharmacophore modelling, virtual screening and molecular docking studies on PLD1 inhibitors.

Lipid metabolism plays a significant role in influenza virus replication and subsequent infection. The regulatory mechanism governing lipid metabolism and viral replication is not properly understood to date, but both Phospholipase D (PLD1 and PLD2) activities are stimulated in viral infection. In vitro studies indicate that chemical inhibition of PLD1 delays viral entry and reduction of viral loads. The current study reports a three-dimensional pharmacophore model based on 35 known PLD1 inhibitors. A sub-set of 25 compounds was selected as the training set and the remaining 10 compounds were kept in the test set. One hundred and twelve pharmacophore models were generated; a six-featured pharmacophore model (AADDHR.57) with survival score (2.69) produced a statistically significant three-dimensional quantitative structure-activity relationship model with r2 = 0.97 (internal training set), r2 = 0.71 (internal test set) and Q2 = 0.64. The predictive power of the pharmacophore model was validated with an external test set (r2 = 0.73) and a systematic virtual screening work-flow was employed showing an enrichment factor of 23.68 at the top 2% of the dataset (active and decoys). Finally, the model was used for screening of the filtered PubChem database to fetch molecules which can be proposed as potential PLD1 inhibitors for blocking influenza infection.

Allergic fungal rhinosinusitis in chronic rhinosinusitis.

BACKGROUND: Rhinosinusitis is the inflammation of nasal and paranasal sinus mucosa and is associated with mucosal alteration ranging from inflammatory thickening or gross nasal polyp formation.The main objective of this study is to determine the prevalence of allergic fungal rhino sinusitis among the patients having chronic rhino sinusitis with or without polyps who under goes functional endoscopic sinus surgery. METHODS: The patient with chronic rhinosinusitis with or without polyp who FESS were studied. Surgical specimens were sent for mycology and histopathological analysis for identification of fungus. RESULTS: Headache 41(82%) and nasal block 45(90%) were the commonest clinical presentation. Out of 50 patients, fungal elements were detected by KOH in 8(16%) of cases and histopathological examination in 11(22%) of cases. CONCLUSIONS: Allergic Fungal Rhinosinusitisis a common disorder in patients with chronic rhinosinusitis, it need different specific tests for the diagnosis, a more specific diagnostic tests are fungus culture, and IgE to fungal antigen and skin test are needed for definite diagnosis.

Semirigid ureteroscopy with pneumatic lithotripsy for ureteral stone.

BACKGROUND: Ureteral stones present with acute loin to groin pain. The objective of this study is to find out the outcome and safety of semi-rigid ureterscopy with pneumatic lithotripsy for treatment of ureteral stones of >30 mm(2) and to assess the impact of size and location on stone free (SF) rate. METHODS: Total 110 patients with isolated ureteral stone size>30 mm(2) were included in this study and treated with pneumatic lithotripsy using 8/9.8 Fr. Semi-rigid ureteroscope (Stiema Germany). Stones were fragmented into 2-3 mm particles and removed. Outcome parameters assessed at 3 months follow up were stone free rate(SF),Efficiency Quotient (EQ), and impact of stone size and site on SF/EQ was also analyzed. Similarly, patient demographics, procedures, patient related parameters and complications were also noted. RESULTS: The overall SF rate at 3 months follow up was 69.33% and efficient Quotient (EQ) 52.52%. The SF/EQ for upper, middle and lower third of ureteral stone was 55/37.67, 61/43.57, 92/84.40 respectively (P-value< 0.001). The SF for stone size 30-110 mm(2) and >110 mm(2) was 78% and 67% respectively. There were no major complications seen. Overall minor complication rate was 5.45 % (minor ureteral perforations-5, urinoma formation 1). CONCLUSIONS: Semi-rigid ureteroscopy with pneumatic lithotripsy is a safe, simple and effective procedure for ureteral stones with excellent success rate for distal ureteral stones. The stone free rate and EQ are statistically significant (P value<0.001) between upper, middle and lower ureteral stones. Stone size has a direct impact on the SF rate and EQ.

Histomorphological spetrum of breast lesions.

BACKGROUND: Cancer of the breast is the second most common cause of cancer in women. Mass in the breast, whether benign or malignant is a cause of anxiety to the patients and the family members. All breast lumps are considered to be carcinomas until proved otherwise and are the causes of concern both for the patient and surgeon. METHODS: This is a retrospective study conducted in Kathmandu Model Hospital for a total duration of three years from August 2007 to August 2010. RESULTS: 114 sample of breast tissue sent for histopathology were studied. Peak incidence of benign lesion was in between 21-30 years and malignant lesions in between 31-50 years. No breast lesions were seen in the first decade of life. Cancer of the breast was seen in 12.28% of cases. Fibroadenoma and fibrocystic disease were the commonest benign lesion and infiltrating ductal carcinoma was the commonest malignant lesion. Specimens from 10 male breasts were received. Gynaecomastia was the most common lesion encountered in males. Infiltrating ductal carcinoma was seen in a 70 year old male. CONCLUSIONS: Breast cancer is one of the commonest causes of breast lump particularly in women and is growing public health problem in Nepal.

Role of CaCO3 alone and CaCO3 plus vitamin D3 in terms of calcium phosphorus product in chronic kidney diseases.

BACKGROUND: CaCO3 alone and CaCO3 plus vitamin D3 metabolites are commonly prescribed in CKD patients. The objective of this study is to analyze the changes in Ca x P product, calcium level and phosphorus level in CKD patients receiving calcium carbonate alone and calcium carbonate with vitamin D3 in combination. METHODS: A prospective, cross sectional study among CKD patients under maintenance hemodialysis two times a week were studied over a period of one year. The patients were divided into two groups receiving oral CaCO3 alone and CaCO3 plus vitamin D3 once a day. The patients were followed for 1 month and result of Ca x P product was analyzed accordingly. RESULTS: Mean decrease of Ca x P product in CaCO3 group is (50.42+/-8.85 to 47 +/-6.63) in one month, p value =0.001(0.6-5) and CI- 95%. There is also significant reduction of phosphorus level in CaCO3 group than CaCO3 plus vitamin D3 group. Mean decrease in phosphorus in CaCO3 group is (5.51+/-0.76 to 5.17+/- 0.05) in one month. P value =0.01(0.14-0.53) and CI 95%. CONCLUSIONS: There is a significant decrease in Ca x P product and phosphorus level was observed in CKD patients taking CaCO3 alone.

Effectiveness and efficiency of Aama Surakshya Karyakram in terms of barriers in accessing maternal health services in Nepal.

BACKGROUND: The Family Health Division along with the MoHP developed a policy that recommended provision of incentives to all delivering mother by removing the parity condition and termed Safe Delivery Incentive Programme (SDIP) to make it more appropriate. The SDIP was branded as AamaSurakshyaKaryakram (ASK). The main objective of the study was to find out the effectiveness and efficiency of AamaSurakshyaKaryakram to address barrier in accessing maternal health services in Nepal. METHODS: An exploratory and cross sectional descriptive study was conducted by quantitative and qualitative tools and techniques. To provide comprehensive coverage, five districts have been selected representing four development (eastern, central, western and far-western) and three (mountain, hill and flat) ecological region were selected. RESULTS: Out of 47 exit client interviews conducted in this study, 51 percent were done in Sunsari, followed by Sarlahi (17%), Dadeldhura (17%), and Arghakhanchi (15%). Most of these mothers (94%) delivered their children in the hospitals, and rest (6%) in PHCCs. Sixty percent mothers were in the age group of 20-25 years, while 45 percent were from Tarai/Madhesi group followed by Brahmins/Chhetries group (34%). Total 70% mothers were found to be literate. 55% mothers were found to be visiting health facilities during labour pain. 2% mothers were visiting heath facilities before labour pain started. Rest mothers were visiting health facilities after one or two days of labour pain. Total 70% mothers were able to reach the health facility within 60 minutes, while 13 percent mothers were able to reach the facility more than 3 hours, and 17% were in between. All mothers who visited PHCCs were able to reach the facility within 60 minutes while analyzing health facility-wise. CONCLUSIONS: Mothers delivered at home as they were not well prepared to go to health facility. Lack of transportation facility hindered for institutional delivery. None of them figured out that there was a provision of transport incentive; they only knew that there was a cash payment, but they didn't know exactly for what specific purpose mothers were receiving such payments. Ask found to be effective and efficient in order to address barriers occurring inside the health facility and financial barrier except geo-graphical barrier in accessing maternal health services in Nepal.

Alpha1 and alpha2 adrenoceptor mediated melanosome aggregatory responses in vitro in Oreochromis mossambica (Peters) melanophores.

Effects of specific and non-specific adrenoceptor agonists and antagonists were examined on the isolated scale melanophores of O. mossambica in physiological Ringer solution. The responses were recorded as melanophore size index. It was observed that adrenaline, nor-adrenaline, phenylpropanolamine, clonidine and phenylepherine induced melanosome aggregation in a dose-dependent manner. Denervation of the fish melanophores increased the sensitivity of the melanophores to adrenaline but not to nor-adrenaline. Phentolamine (3.55 x 10(-5) M), prazosin (2.38 x 10(-5) M) and yohimbine (2.821 x 10(-5) M) significantly inhibited the aggregatory responses of the fish melanophores to adrenaline, nor-adrenaline, clonidine and phenylepherine. The blocking effect of yohimbine was significantly higher than that of prazosin. It is concluded that the effect of adrenaline is directly mediated through the receptors and alpha2 adrenoceptors are predominantly involved in the aggregatory responses of this fish melanophores, while alpha1 adrenoceptors presence has been indicated.

The effect of two different dental gels and a mouthwash on plaque and gingival scores: a six-week clinical study.

AIM: To evaluate the clinical efficacy of two gel formulations containing chlorhexidine gluconate and neem extract with a commercially available chlorhexidine gluconate mouthwash. METHOD: An open labelled randomised six-week clinical study with parallel group design in 48 subjects divided into four groups. Plaque accumulation and gingival condition were recorded using plaque index and gingival index. On the basis of mean baseline plaque and gingival scores, subjects were allocated to four different groups, using their assigned products twice a day, before bed and after breakfast. Plaque and gingival scores were recorded after three and six weeks. RESULTS: Mean plaque and gingival scores were reduced over the six-week trial period for experimental and control groups. Chlorhexidine gluconate gel reduced the plaque and gingival scores significantly more (p<0.05) than the chlorhexidine gluconate mouthwash. Neem extract gel also showed significant (p<0,05) reduction in plaque and gingival scores when compared with the control group. But there was no significant difference between the groups treated with chlorhexidine gel and neem extract gel. CONCLUSION: The results of this clinical study indicate that better therapeutic efficacy can be achieved using gels for treating oral infections than conventional treatments using mouthwash.

Maternal and child health services in rural Nepal: does access or quality matter more?

This study seeks to establish the relative importance of service access and quality on utilization of preventive health services in the western and middle-western Hill region of Nepal. Access was measured in terms of travel time to the nearest health post and coverage by outreach workers. The quality of static services was defined in structural terms: physical infrastructure, number of staff, availability of drugs and holding of special maternal and child health clinics. The initial analysis showed that no single indicator of quality was of overriding importance and therefore an overall quality index was constructed. After adjustment for access and for socioeconomic characteristics of families and communities, a very pronounced relationship between overall structural quality of the nearest health post and service uptake persisted. The adjusted odds of using some form of antenatal service were 6.6 times higher in the catchment areas of high quality posts than in areas served by low quality posts. The corresponding figure for receipt of BCG vaccination is 8.1. By comparison, the effects of travel time to the nearest health post are modest. Uptake of services is about twice as high when there is a health post in the community. Regular monthly visits by outreach workers also had a marked effect on service utilization. These results suggest that investment in the quality of health posts is more important than further increases in their number and that a further expansion of outreach services is a priority.