Silver nanoparticles (AgNPs) induced impairment of in vitro pollen performance of Peltophorum pterocarpum (DC.) K. Heyne.

Increasing use of silver nanoparticles (AgNPs) in myriad applications including electronics, medicines and agriculture has led to serious concerns regarding its release to plant ecosystems. Over the years, numerous studies have demonstrated the toxic impact of AgNPs in a variety of cell and tissue systems involved in vegetative growth across a wide range of plant species. However, assessing their impact on haploid phase of plant life cycle was restricted only to a study with Kiwifruit. In this study, in vitro pollen performance of Peltophorum pterocarpum at two endpoints i.e., germination and tube growth was assessed to evaluate the impact of nanoparticulate or ionic form of silver. Increasing concentrations of AgNO3/AgNPs significantly reduced the pollen germination and retarded the tube growth. The EC 50 values indicated a more potent toxic effect of AgNPs than AgNO3 on pollen germination as well as tube growth. Impairment of pollen performance was more pronounced at the stage of emergence of pollen tube. Extensive alterations in the muri and lumen of exine as revealed through SEM analysis and subsequent blockage of germpore might disrupt the emergence of pollen tube. The dynamics of pollen tube growth was analyzed with polynomial models of different degrees. A high degree of polynomial, the quintic model was able to approximate the real data points with highest coefficient of determination and smallest RMSE, compared to other models. An oscillating pattern of tube growth was portrayed with the passage of time in all the treatments that fits well with the established mechanistic oscillatory model of tube growth. It appears that exposure to AgNO3/AgNPs inhibited pollen germination and retarded tube growth without affecting the oscillatory behavior of tip-growth.

Chemometric approach based characterization and selection of mid-early cauliflower for bioactive compounds and antioxidant activity.

The present study was aimed to analyse bioactive compounds (total phenolics, ascorbic acid and sinigrin) and antioxidant activity in 14 mid-early cauliflower genotypes. Significant differences (pb 0.05) were observed among the genotypes for all bioactive compounds and antioxidant activity. Total phenolics content of curd were ranged from 20.36 to 48.93 mg gallic acid equivalent (GAE) 100 g-1 fresh weight (FW) which showed 2.5 times variation. The ascorbic acid content was maximum in DC522 (88.53 mg 100 g-1 FW) followed by Pusa Sharad (65.64 mg 100 g-1 FW) while minimum in DC310 (39.62 65.64 mg 100 g-1 FW). Wide variation was observed for cupric reducing antioxidant capacity and ferric reducing antioxidant power ranging from 9.04 to 20.83 mg GAE 100 g-1 FW and 13.11 to 26.31 mg GAE 100 g-1 FW, respectively. Sinigrin was found to be highest in DC306 (39.50 µmol 100 g-1 FW) for leaf and in DC326 (36.93 µmol 100 g-1 FW) for curd sample. The cauliflower genotypes were classified based on chemometric approaches namely principal component analysis (PCA) and agglomerative hierarchical clustering (AHC). The first two principal components (PC1 and PC2) explained 50.62% and 23.28% of total variance, respectively. The AHC as revealed by heat map classified cauliflower genotypes into four main groups based on measured traits. The information is useful for developing varieties and/or hybrids rich in bioactive compounds and antioxidant activity.

Enzymatic hydrolysis of whey and its analysis.

An attempt was made to hydrolyze proteins and lactose in whey to improve the nutritive value of this byproduct, and extend its application as an ingredient to healthy beverages. Flavourzyme in different concentrations was used at pH 7.0 to hydrolyze protein at 50 °C. pH stat method, SDS-PAGE and RP HPLC-MS were used to evaluate degree of protein hydrolysis, pattern of peptide formation and characterize smaller peptides in hydrolysate, respectively. Higher concentration of enzymes produced more number of small peptides. Protein hydrolysate was again hydrolyzed at 30 °C with ß-galactosidase at pH 5.5 to hydrolyze lactose. HPLC analysis indicated the degree of lactose hydrolysis and number of tri/poly saccharides formed due to varied enzyme concentration. Results from the experiment can be utilized to formulate healthy whey beverages for specific purpose.

Plant Pathogenic Microbial Communication Affected by Elevated Temperature in Pectobacterium carotovorum subsp. carotovorum.

Gram-negative plant pathogenic bacteria regulate specific gene expression in a population density-dependent manner by sensing level of Acyl-Homoserine Lactone (HSL) molecules which they produce and liberate to the environment, called Quorum Sensing (QS). The production of virulence factors (extracellular enzyme viz. cellulase, pectinase, etc.) in Pectobacterium carotovorum subsp. carotovorum (Pcc) is under strong regulation of QS. The QS signal molecule, N-(3-oxohexanoyl)-L-Homoserine Lactone (OHHL) was found as the central regulatory system for the virulence factor production in Pcc and is also under strict regulation of external environmental temperature. Under seven different incubation temperatures (24, 26, 28, 30, 33, 35, and 37 °C) in laboratory condition, highest amount of OHHL (804 violacein unit) and highest (79 %) Disease Severity Index (DSI) were measured at 33 °C. The OHHL production kinetics showed accumulation of highest concentration of OHHL at late log phase of the growth but diminution in the concentration occurred during stationary phase onwards to death phase. At higher temperature (35 and 37 °C) exposure, OHHL was not at detectable range. The effect of temperature on virulence factor production is the concomitant effect of HSL production and degradation which justifies less disease severity index in cross-inoculated tomato fruits incubated at 35 and 37 °C. The nondetection of the OHHL in the elevated temperature may because of degradation as these signal molecules are quite sensitive and prone to get degraded under different physical factors. This result provides the rationale behind the highest disease severity up to certain elevated temperature and leaves opportunities for investigation on mutation, co-evolution of superior plant pathogen with more stable HSL signals-mediated pathogenesis under global warming context.

Prey preferences of aquatic insects: potential implications for the regulation of wetland mosquitoes.

Wetlands are potential sites for mosquito breeding and are thus important in the context of public health. The use of chemical and microbial controls is constrained in wetlands in view of their potential impact on the diverse biota. Biological control using generalist aquatic insects can be effective, provided a preference for mosquito larvae is exhibited. The mosquito prey preferences of water bugs and larvae of odonate species were evaluated using chironomid larvae, fish fingerlings and tadpoles as alternative prey. Manly's selectivity (αi ) values with 95% confidence intervals (CIs) were estimated to judge prey preference patterns. Multivariate analysis of variance (manova) and standardized canonical coefficients were used to test the effects of density on prey selectivity. The αi values indicated a significant preference (P < 0.05) in all of the insect predators tested for mosquito larvae over the alternative prey as a density-dependent function. On a comparative scale, chironomid larvae had the highest impact as alternative prey. In a multiple-prey experiment, predators showed a similar pattern of preference for mosquito larvae over alternative prey, reflecting a significant (P < 0.05) niche overlap. The results suggest that, in a laboratory setting, these insect predators can effectively reduce mosquito density in the presence of multiple alternative prey.

Urinary tuberculosis presented as isolated bladder lesion - a case report.

Extra-pulmonary Tuberculosis (EPTB) may affect all organs of the body with varied presentations. Genitourinary tuberculosis (GUTB) carries importance for its morbidity, though it is an uncommon form of TB. A widow of 45 years was admitted with several episodes of painless haematuria and recently developed urinary incontinence. Diagnosis of urinary bladder tuberculosis was made only by histopathology from bladder lesion with supportive evidence of few nonspecific constitutional symptoms and positive family history of pulmonary tuberculosis (PTB) and persistent sterile pyuria. Upper urinary tract involvement was not found. Category 1 anti-TB treatment was started. With this treatment recovery of the patient is satisfactory and symptoms are disappearing except for the incontinence. Urinary tuberculosis should be ruled out in a case of painless haematuria, repeated sterile pyuria.

Association of Triglyceride and C-reactive Protein Level with Severity of Angiographically Defined Coronary Artery Disease.

Coronary artery disease (CAD) is considered as a major cause of morbidity and mortality worldwide. Inflammatory cytokines play an important role in the pathogenesis and progression of atherosclerosis. The aim of the study was to find out the association of C-reactive protein (CRP) and triglyceride (TG) level on the severity of CAD in patients with ischemic heart disease (IHD). This cross-sectional study was performed in the Department of Cardiology, National Institute of Cardiovascular Diseases, Dhaka, Bangladesh during the period of March 2018 to February 2021. Total 431 patients with ischemic heart disease were enrolled after taking informed written consent. CRP values were categorized into normal (<6 mg/L), borderline (6-10 mg/L) and high (>10mg/L) and TG level were categorized into normal (<150 mg/dl), borderline (150-199mg/dl) and high (≥200 mg/dl). Patients with ischemic heart disease (IHD) were stratified according to CRP value and TG level. Severity of CAD was assessed by the Gensini score. Most of the patients (33.4%) belonged to age 51-60 years. The mean age was 51.31±10.30 years. The majority (74.5%) of patients were male. Among risk factors, the highest 205(47.6%) patients were smokers followed by hypertension 190(44.1%) and diabetes mellitus 175(40.5%). The association of TG and CRP with the whole spectrum of IHD was found statistically significant (p<0.05). Severe CAD was found higher in high TG and high CRP level group compared with the other groups and was statistically significant. Inflammation assessed by high CRP and hypertriglyceridemia associated with the risk and severity of CAD.

Endovascular Aneurysm Repair for Infrarenal Abdominal Aortic Aneurysm: New Horizon in Endovascular Surgery in Bangladesh.

Abdominal aortic aneurysm remains mostly asymptomatic. It is usually detected incidentally with imaging studies. Here we present a 55 years old hypertensive, non smoker, non diabetic, male patient who was diagnosed as a case of infrarenal abdominal aortic aneurysm. He was treated by endovascular means using endograft without laparatomy. Endografts were deployed through bilateral femoral artery cut down technique under general anesthesia. Completion angiogram following this endovascular aneurysm repair (EVAR) technique revealed good technical success with no endoleak. This hybrid procedure was performed in a cathlab having surgical instruments in hand. Three years after the procedure, patient is doing well.

Congenital stenosis in the descending colon causing intestinal obstruction in a one and half years male child.

A one and half years male child presented with constipation with severe colicky abdominal pain, bilious vomiting & abdominal distension. He had history of recurrent bouts of constipation followed by gastroenteritis since birth for which he had taken symptomatic treatment & sometimes remained symptom free but he had no other significant history or associated condition. In laboratory investigations, barium enema study of large gut result simulates to Hirschsprung's disease but suction rectal biopsy revealed normal rectal tissue texture. So, consideration of diagnostic tools along with patient's general condition decision was taken for diagnostic laparotomy & peroperatively the child was diagnosed as a case of intestinal obstruction due to congenital colonic stenosis in the descending colon. After resection of stenotic segment and end to end anastomosis, histopathologycal examination of resected stenosed colon was done & it was finally proved as congenital stenosis in the descending colon. The post operative period of the patient was uneventful and he was discharged on 7th postoperative day & followed up upto 6 months. He had been found alright without any complain. Here we tried to high light that the congenital colonic stenosis as a rare, but might be a possible cause of partial/complete intestinal obstruction from newborn to older children in any part of the colon & that should kept in mind for avoiding diagnostic dilemma & proper management of patient.

Surgical outcome of laparoscopic and open surgery of pediatric inguinal hernia.

Inguinal hernia repair is one of the most frequently performed surgical procedures in infants and young children. This prospective comparative study was conducted with initial experience in the department of pediatric surgery, Dhaka Shishu (children) hospital during the period of July 2007 to August 2008. We enrolled 62 children undergoing surgery for inguinal hernia, of which 30 underwent laparoscopic procedure (bilateral in 21, unilateral 9) and 32 open procedures (bilateral in 5, unilateral in 27). Mean±SD patient age was 5.92±2.11 months in laparoscopic group and 6.63±2.64 months in open group (p=0.264), 3 months to 5 years in both groups. Patients were studied under variables of operative time, duration of postoperative hospital stay & post operative complications. During laparoscopy a contralateral patent processus vaginalis of ≥2cm was noted and repaired peroperatively in 18 out of 27 children (66%), who were initially diagnosed as unilateral hernia. For unilateral repair mean±SD operative time was significantly longer in Group A (62.63±52.75) minutes compares to the Group B (29.37±9.40), p<0.001. On the contrary, for bilateral repair Mean±SD operative time was comparable between the two groups (64.65±49.70) minutes for laparoscopy & (35.65±11.53 minutes) for open herniotomy & P=0.01, that was not remarkably significant. The mean±SD post operative length of hospital stay (in hours) 36.00±32.7 hours in Group A compared to 29.97±11.82 hours in Group B which was not statically significant (p=0.342). The mean±SD follow up was 24.5±10.5 months in laparoscopic group (Group A) & 22.5±10.5 months in open group (Group B), p=0.251. Regarding post operative complication, in this study, contra lateral metachronous inguinal hernia (CMIH) manifested in none of the patient out of 27 (total unilateral repaired number) patients in laparoscopic group but contrary to this in open group 2 patients out of 27 had developed CMIH & p value was <0.05, which is statistically significant. There were 2 cases of scrotal hydrocele out of 30, observed in Group A whereas 1 case out of 32 in Group B, p=0.49, which was statistically insignificant. The scrotal hydrocele was lasted only for 2 days & resolved spontaneously. About recurrence after operation, our study noted that, 1 case (3.3%) out of 30 in laparoscopic group and 2 cases (6%) out of 32 in open surgery group had developed recurrent inguinal hernia in about one year follow up where p value was 0.459, & it was statistically insignificant. In this study, none of the patient had developed post operative testicular atrophy (due to any vas or vascular injury) or testicular ascend. So, overall this study result implies that, Laparoscopic herniotomy might be a safe and effective option as open herniotomy for the treatment of inguinal hernia in children but which one would be superior or best option it requires a large series of randomized trial.

Congenital duodenal web (wind-soak variety) in the fourth part of the duodenum causing obstruction in a female child.

Delayed presentation of Duodenal Obstruction is a great diagnostic dilemma due to non-specific, varied & wide spectrum presentation. In this study, a 6 years female child presented with recurrent, intermittent, colicky abdominal pain with bilious vomiting, and occasional constipation from 9 months of her age, without having any significant family history or associated condition. She was initially diagnosed as a case of recurrent small bowel obstruction due to atypical variant of malrotation. But, after laparotomy, she was finally diagnosed as a case of recurrent duodenal obstruction due to Congenital Duodenal Web (Wind-Soak Variety) with a central hole in the fourth part of the duodenum. After uneventful recovery of post operative period the patient was discharged at 7th postoperative day & followed up upto 3 months. She had been found alright without any complication.

Non-Hodgkin's lymphoma is a pathological lead point causing large gut (colo-colic varity) intussusception.

Intussusception secondary to Primary Non-Hodgkin lymphoma presenting colo-colic variety is a very rare clinical entity and sometimes causing diagnostic dilemma due to non-specific, varied & wide spectrum presentation. In this study, a 9 years female child presented with recurrent, intermittent, colicky abdominal pain with occasional bilious vomiting, along with a left illiac fossa swelling & occasional per rectal bleeding and constipation for 3 months was clinically diagnosed as a case of recurrent obstructing intussusception. At laparotomy, a colo-colic intussusception with prolapsed intussusception was marked & finally on histopathology, she was diagnosed as a case of colo-colic variety of intussusception due to primary Non-Hodgkin lymphoma- a pathological lead point in mid transverse colon. After uneventful recovery of post operative period she was treated with combination chemotherapy accordingly & follow up was given up to 5 years. She had been found alright without any recurrence or organ involvement. The study focused on the avoidance of unusual delay in diagnosis as well as in proper management of rare variants of intussusception.

Congenital urogenital sinus anomaly without Adrenal Hyperplasia.

Urogenital sinus anomaly is a mal-development of female urogenital system, usually associated with Congenital Adrenal Hyperplasia and may varied in presentation according to embryologic separation and length of sharing of common channel between vagina and urethra. We report a case of pure urogenital sinus anomaly of 2.5 years female child without any feature of Congenital Adrenal Hyperplasia or any other associated anomalies which is quite uncommon. The patient was diagnosed with thorough physical, biochemical, radiological and endoscopic evaluation. She had clitiromegaly, very poorly developed fused Labia minoras with a central hole, the length of common channel was about 2.5 cm and the level of vaginal confluence was at the mid portion of common channel. After in general counseling to parents, according to their desire she was operated. We performed Labialo-clitoro-vagino-urothroplasty and from post operative period to till now (after 3 months of operation) she is uneventful. Both functionally and cosmetically she is sound and her parents are also happy.

Laparoscopic versus open pyloromyotomy for infantile hypertropic pyloric stenosis: an early experience.

This prospective comparative study was conducted with an initial experience in the Department of Pediatric Surgery, Dhaka Shishu (Children) Hospital during the period of December 2007 to January 2009, with the infants of 2-12 weeks age, diagnosed as Hypertrophic pyloric stenosis. Patients selection was done by simple random technique by means of lottery. For open pyloromyotomy conventional method & for laparoscopic pyloromyotomy three trocher techniques was applied. In this study, among 60 cases with infantile hypertrophic pyloric stenosis, 30 cases were finally selected for analysis irrespectively both in laparoscopic (Group A) & in open pyloromyotomy (Group B) group. Patients were studied under variables of operative time, required time of full feeds after operation, post operative hospital stay & both per and post operative complications. Regarding operative time, in Group A, mean±SD operating time (in minutes) was 61.59±51.73 whereas in Group B it was 28.33±8.40 & P value was 0.001. The result was statistically significant. The mean±SD time (in hours) of full feeds (ad libitum) was 35.00±31.70 hours in Group A compared to 28.95±10.99 hours in Group B and P value was found 0.342ns which was not statistically significant. On study of total length (in days) of post operative hospital stay, mean±SD was 3.09±2.25 & 2.58±1.15days in laparoscopic group & open pyloromyotomy group respectively. The p value was 0.355ns, which was statistically insignificant. Again, on study of complications, per operatively 6(19.5%) patients had developed haemorrage, 1(3.33%) had mucosal perforation & 4(13.36%) had developed duodenal serosal injury in laparoscopic group whereas only 1(3.33%) patient in open pyloromyotomy group had nothing else except simple hemorrhage. The p value (0.051ns) was also statistically insignificant. In regard to post operative complications, 2(6.6%) patients had developed wound hematoma, 2(6.6%) had wound infection, 1(3.33 %) had developed wound dehiscence and incisional hernia respectively in Group A. But in group B there was no subject with any complication. This result was also statistically insignificant. So, the overall study results denote that, laparoscopic pyloromyotomy would not be considered as a superior procedure or as safe as that of traditional open pyloromyotomy for the beginners.

Pharmacokinetic-pharmacodynamic equivalence of three gliclazide formulations in healthy human male subjects.

AIMS: To find out the pharmacokinetic (PK) and pharmacodynamic (PD) parameters for assessing the bioequivalence of three marketed products. To study the relationship between the pharmacokinetics of gliclazide and pharmacodynamic effect in healthy male volunteers. METHODS: This was an open label, balanced, randomized, 3-treatment, 3-sequence, 3 period, single-dose, cross-over bioavailability study in which 18 healthy adults were randomized to receive gliclazide 80 mg with 7 days wash out between treatments. The drug was administered with 240 ml of 20% glucose solution after a 10 h overnight fasting. Pharmacokinetic parameters like t(max), C(max), AUC(0-t), AUC(0-∞), AUC(0-t) / AUC(0-∞) and t(1/2) and pharmacodynamic parameters like maximum effect (minimum glucose level in the body, C(minglu)), time to minimum glucose level in the body (T(cminglu)) and partial AUC were calculated for all the products. RESULTS: The values for mean ± SD for age, height and weight of the volunteers were 28.00 ± 22.68, 165.78 ± 5.56 and 56.78 ± 13.37 respectively. There were total 4 withdrawn subjects and 1 drop out. Within batch accuracy of the method were in the range of 95.5 - 101.7%, 99.1 - 106.1% and 96.2 - 104.2% for three consecutive batches. The 90% CI for log transformed data of the PK and PD were within the acceptance range of 80.0 - 125.0%. CONCLUSIONS: This population PKPD analysis has characterized the relationship between the exposure to gliclazide and its hypoglycemic effect. The test products A & B compared to reference product R were bioequivalent on the basis of pharmacokinetic and pharmacodynamic parameters. Finally it is recommended that the more costly product R can be safely switched with less costly products i.e. A and B.

Comparison of post operative morbidity between laparoscopic and open appendectomy in children.

This prospective comparative study was conducted in the department of Pediatric Surgery, Dhaka Shishu (children) Hospital during the period of June 2007 to September 2008 with the children of <12 years, diagnosed as acute Appendicitis. Patient selection was done by simple random technique by means of lottery. For open Appendectomy (OA) conventional method & for Laparoscopic Appendectomy (LA) 3 trocher technique was applied. Data was analyzed with the help of SPSS version 10. In this study 60 cases with acute Appendicitis including both gender were studied by two groups, group-A include 30 cases for laparoscopic and group-B include 30 cases for open appendectomy. Postoperative pain was assessed in both groups by using FLACC scale and compared at 1st 6-hours, 24 hours, 72 hours, 96 hours & at day 7. At 1st 6-hours, most of the children 24(80%) of group A had moderate pain whereas 17(56.7%) children of group B had severe pain (p<0.001). At 24 hours most of the patient 17(56.7%) of group A had mild pain compared to 27 (90%) patients of group B had moderate pain (p<0.0001). At 48 hours in group A most of the children 23(76.7%) had mild pain compared to moderate pain in 18(60%) children of group B (p<0.0001). Subsequently at 72 hours and at 96 hours most of the patients of LA group were free of pain compared to OA group. At final follow-up on day 7, 29(96.7%) children of group A had no pain compared to 26(86.7%) of group B. Regarding analgesics requirement both qualitative & quantitative requirements of analgesics were less in LA group than OA group. About post operative wound infection in group A only 1(3.3%) case had developed post operative wound infection whereas in group B 7(23.3 %) cases had. The mean (+/-SD) of post operative length of hospital stay was 52.00+/-11.62 (range 48-96) hours for group A and 76.00+/-12.74 (range 48-96) hours for group B children (p<0.001). Laparoscopic Appendectomy is more effective, preferable & superior procedure than that of open Appendectomy to reduce the post operative morbidity in children undergone appendectomy for acute appendicitis.

Tuberculosis of the central nervous system.

Tuberculosis can involve any organ system of the body. Although rare tuberculosis of nervous system (NS) is not uncommon in our country. In the nervous system tubercle bacilli can cause tuberculous meningitis, abscess , tuberculoma in brain & spinal cord. Untreated Central Nervous System (CNS) tuberculosis is devastating. Early diagnosis & prompt treatment of NS is essential to avoid morbidity & mortality. Tubercle bacilli causes chronic caseating granulomatous lesion. Tubercular meningitis presents with fever, headache, neck stiffness & cranial nerve palsy. Tuberculoma may present with headache, seizure and focal deficit. In the spinal cord tuberculoma or tubercular abscess may result in para paresis or quadri-paresis. For diagnosis of nervous system tuberculosis CSF analysis and neuroimaging are important. CSF cell count, Gram staining, Culture and Polymerase Chain Reaction (PCR) are helpful for diagnosis. Imaging helps in the diagnosis of tuberculoma and tubercular abscess. Computed tomography (CT) guided Fine Needle Aspiration for Cytology (FNAC) helps to establish the histopathological diagnosis. Use of combination antitubercular drugs for long period (12-18 months) is necessary to treat nervous system tuberculosis.

Chromium III exposure inhibits brain Na+K+ATPase activity of Clarias batrachus L. involving lipid peroxidation and deficient mitochondrial electron transport chain activity.

The present study elucidated the role of lipid peroxidation and diminished mitochondrial electron transport chain activity in partial dysfunction of brain Na+K+ATPase of Clarias batrachus exposed to chromium III ions. The fish were exposed to 10% and 20% of the derived 96 h LC50 value, 5.69 mg/L and 11.38 mg/L, respectively, and sampled on 20, 40 and 60 days. Exposure to chromium III on fish brain demonstrated an increased lipid peroxidation, production of protein carbonyl and reactive oxygen species and loss of protein thiol groups in synaptosomal fraction with decreased activity of Na+K+ATPase, partial inactivation of mitochondrial electron transport chain activity and energy depletion.

Combining molecular docking and molecular dynamics studies for modelling Staphylococcus aureus MurD inhibitory activity.

The ATP-dependent bacterial MurD enzyme catalyses the formation of the peptide bond between cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine and D-glutamic acid. This is essential for bacterial cell wall peptidoglycan synthesis in both Gram-positive and Gram-negative bacteria. MurD is recognized as an important target for the development of new antibacterial agents. In the present study we prepared the 3D-stucture of the catalytic pocket of the Staphylococcus aureus MurD enzyme by homology modelling. Extra-precision docking, binding free energy calculation by the MM-GBSA approach and a 40 ns molecular dynamics (MD) simulation of 2-thioxothiazolidin-4-one based inhibitor $1 was carried out to elucidate its inhibition potential for the S. aureus MurD enzyme. Molecular docking results showed that Lys19, Gly147, Tyr148, Lys328, Thr330 and Phe431 residues are responsible for the inhibitor-protein complex stabilization. Binding free energy calculation revealed electrostatic solvation and van der Waals energy components as major contributors for the inhibitor binding. The inhibitor-modelled S. aureus protein complex had a stable conformation in response to the atomic flexibility and interaction, when subjected to MD simulation at 40 ns in aqueous solution. We designed some molecules as potent inhibitors of S. aureus MurD, and to validate the stability of the designed molecule D1-modelled protein complex we performed a 20 ns MD simulation. Results obtained from this study can be utilized for the design of potent S. aureus MurD inhibitors.

Influence of grape juice and orange juice on the pharmacokinetics and pharmacodynamics of diltiazem in healthy human male subjects.

OBJECTIVE: The objective was to study the effect of grape juice and orange juice on the pharmacokinetics (PK) and pharmacodynamics (PD) of diltiazem in healthy human volunteers. METHODOLOGY: The study design was open-label, balanced, randomized, 3-period, single-dose and crossover. A group of 12 healthy, adult, male human volunteers received a single oral dose of diltiazem 180 mg extended release capsule on three different occasions: with 200 ml of water, with 200 ml of grape juice and with 200 ml of orange juice in random order. A washout period of 7 days was kept between each study period. Serial blood samples were collected up to 24 h post dose and assayed for diltiazem using a specific and validated HPLC method. Blood pressure (BP) and ECG measurements were done at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 h post dose. Analysis of variance was carried out using logarithmic transformations of AUC and Cmax as well as nontransformed tmax. RESULTS: No significant change was observed in heart rate and BP. The median tmax was identical in all three occasions. The 90% CI of the Cmax ratios for orange juice/water were 104.59 - 114.86 and for grape juice/water were 93.91 - 103.13. Similarly, the 90% CI of the AUC0-inf ratios for orange juice and grape juice vs. water were 103.68 - 119.83 and 88.56 - 104.06, respectively. Since these values fall within the bioequivalence criteria of 80 - 120% limits, our study demonstrates absence of interaction of diltiazem with grape juice or orange juice. CONCLUSIONS: There is no significant influence of grape juice or orange juice on the pharmacokinetics and pharmacodynamics of diltiazem.