Differential expression of miRNAs and related mRNAs during heat stress in buffalo heifers.

The present experiment was aimed to study differential expression of miRNAs and related mRNAs during heat stress (HS) in buffalo heifers. Twelve Murrah buffalo heifers aged between 1.5 and 2.0 years, weighting between 250 and 300 Kg were randomly assigned into two equal groups. The animals were kept in the psychrometric chamber under Thermo-neutral (TN; THI = 72) and HS (THI = 87-90) conditions for 6 h every day between 1000 and 1600 h for 21 days. The blood sampling was done at 1500 h on 15th day of the experiment and physiological parameters viz. pulse rate (PR), respiratory rate (RR) and rectal temperature (RT) were recorded at 1500 h on day -5, -3, -1, 0, +1, +3, +5 with respect to blood sampling. PBMCs were used for extraction of miRNAs and total RNA; and first strand cDNA was synthesized. qPCR was performed for relative gene expression studies. Physiological, hematological (erythrocytic indices), biochemical (triglycerides, urea, ALT, AST, LDH), redox (SOD, ROS) and endocrine parameters (T4) altered significantly (P < 0.05) during HS as compared to TN. Out of eight targeted miRNAs only four were expressed in buffalo heifers. The relative expression of bta-mir-142, bta-mir-1248 and bta-mir-2332 was significantly (P < 0.05) up-regulated whereas expression of bta-mir-2478 was significantly (P < 0.05) down-regulated during HS as compared to TN. The relative expression of the predicted target genes i.e. HSF1, HSP60, HSP70, HSPA8 and HSP90 were significantly (P < 0.05) up-regulated whereas HSF4 expression was significantly (P < 0.05) down-regulated during HS as compared to TN. It can be concluded that a THI of 87-90 could lead to a moderate HS in buffalo heifers. Differential expression studies of miRNAs and related mRNAs in present study deciphers the role of miRNAs in the heat tolerance in buffalo heifers.

Appropriate THI model and its threshold for goats in semi-arid regions of India.

The present study was attempted to identify an appropriate THI model and threshold THI for goats of semi-arid regions of India. Sixty non-pregnant goats each from Jamunapari and Barbari breeds were selected for the study. The study was conducted from last week of February to first week of June, during which average THI ranged between 53 and 92. Pulse rate (PR), respiration rate (RR) and rectal temperature (RT) were recorded at 1430 h on alternate days from six goats of each breed randomly during the experiment. Nine THI models were used to calculate THI. An appropriate THI model was predicted on the basis of correlation between THIs calculated from each model and physiological responses. The data of physiological parameters were linked to the THI calculated from identified THI model and threshold THI for each parameter was determined using segmented regression analysis (SegReg Software). The THI models; THI1{(1.8 × Tdb+32)-[(0.55-0.0055 × RH) × (1.8 × Tdb-26.8)]} and THI8{(0.8 × Tdb)+[(RH/100) × (Tdb-14.4)]+46.4)} were found to be equally appropriate for assessing environmental heat stress. Threshold THIs with respect to PR, RR and RT in Jamunapari goat were 71.78, 75.14 and 85.94, respectively and in Barbari goats, threshold THIs for PR and RR were 79.48 and 84.40, respectively. A threshold THI could not be identified for RT in Barbari goats. It can be concluded that THI1 and THI8 were the appropriate THI models for measuring environmental heat stress in goats. Results suggested that PR is the first physiological parameter which alters after the onset of heat stress and is followed by changes in RR and RT. On the basis of differential threshold THIs, it can be concluded that Barbari is better adapted than Jamunapari goats in semi-arid regions of India.

Models for anti-tumor activity of bisphosphonates using refined topochemical descriptors.

An in silico approach comprising of decision tree (DT), random forest (RF) and moving average analysis (MAA) was successfully employed for development of models for prediction of anti-tumor activity of bisphosphonates. A dataset consisting of 65 analogues of both nitrogen-containing and non-nitrogen-containing bisphosphonates was selected for the present study. Four refinements of eccentric distance sum topochemical index termed as augmented eccentric distance sum topochemical indices 1-4 [formula: see text] have been proposed so as to significantly augment discriminating power. Proposed topological indices (TIs) along with the exiting TIs (>1,400) were subsequently utilized for development of models for prediction of anti-tumor activity of bisphosphonates. A total of 43 descriptors of diverse nature, from a large pool of molecular descriptors, calculated through E-Dragon software (version 1.0) and an in-house computer program were selected for development of suitable models by employing DT, RF and MAA. DT identified two TIs as most important and classified the analogues of the dataset with an accuracy of 97% in training set and 90.7% in tenfold cross-validated set. Random forest correctly classified the analogues with an accuracy of 89.2%. Four independent models developed through MAA predicted the activity of analogues of the dataset with an accuracy of 87.6% to 89%. The statistical significance of proposed models was assessed through intercorrelation analysis, specificity, sensitivity and Matthew's correlation coefficient. The proposed models offer a vast potential for providing lead structures for development of potent anti-tumor agents for treatment of cancer that has spread to the bone.

Models for cannabinoid-1 receptor antagonistic activity of substituted 2-(3-pyrazolyl)-1,3,4-oxadiazoles.

Antagonism of cannabinoid receptor-1 has emerged as a most promising therapeutic target for the development of anti-obesity drugs. In the present study, an in silico approach using decision tree, random forest and moving average analysis has been applied to a data set comprising of 76 analogues of substituted 2-(3-pyrazolyl)-1,3,4-oxadiazoles for development of models for prediction of antagonistic activity of cannabinoid receptor-1. A total of 46 2D and 3D molecular descriptors of diverse nature were employed for decision tree and random forest analysis. The values of majority of these descriptors for each analogue involved in the dataset were computed using E-Dragon software (version 1.0). Random forest correctly classified the analogues into active and inactive with an accuracy of 95%. A decision tree was also utilized for determining the importance of molecular descriptors. The decision tree learned the information from the input data with an accuracy of 99% and correctly predicted the cross-validated (10 fold) data with an accuracy up to 90%. Finally, three molecular descriptors of diverse nature (including best descriptor identified by decision tree analysis) were subsequently used to build suitable models using moving average analysis. These models resulted in the prediction of cannabinoid receptor-1 antagonistic activity with an accuracy of 95-96%. High predictability of proposed models offer vast potential for providing lead structures for the development of potent cannabinoid receptor-1 antagonists for the treatment of obesity.

Models for prediction of (V)600(E)BRAF and melanoma cells growth inhibitory activities of pyridoimidazolones.

Targeted inhibition of activated BRAF mutation has emerged as a most promising and putative therapeutic approach for the anticancer drug development. In the present study, an in-silico approach using decision tree and moving average analysis has been applied to a data set comprising of 43 analogues of pyridoimidazolones for development of models for prediction of both (V)600(E)BRAF and melanoma cells (BRAF WM266.4) growth inhibitory activities. A decision tree was mainly employed for determining the importance of molecular descriptors (n=46). The value of majority of these descriptors for each analogue in the dataset was computed using E-Dragon software (version 1.0). The decision tree learned the information from the input data with an accuracy of 98% and correctly predicted the cross-validated (10-fold) data with accuracy up to 79%. A total of three non-correlating descriptors, identified best by the decision tree analysis, were subsequently utilized for development of suitable models using moving average analysis. These proposed models resulted in the prediction of (V)600(E)BRAF inhibitory activity (IC50) and melanoma cells growth (SRB GI50) inhibitory activity with an overall accuracy of ≥90%. The statistical significance of models/descriptors was assessed through intercorrelation analysis, sensitivity, specificity and Matthew's correlation coefficient.

Regulation of adiponectin release and demonstration of adiponectin mRNA as well as release by the non-fat cells of human omental adipose tissue.

OBJECTIVE: Adiponectin is an adipokine produced by adipose tissue. The present studies examined the in vitro release of adiponectin by human omental adipose tissue explants as well as the mRNA content of freshly isolated non-fat cells and adipocytes plus cultured preadipocytes and adipocytes derived from omental fat. RESULTS: The release of adiponectin was reduced while that of interleukin-8 (IL-8) was enhanced in tissue explants from morbidly obese women. The release of adiponectin was also reduced by one-third in explants from morbidly obese diabetic women while that of IL-8 was unaffected by diabetes. The release of adiponectin was enhanced by insulin and by inhibition of endogenous tumor necrosis factor (TNFalpha) using etancercept. Adiponectin was released in appreciable amounts by the undigested matrix obtained by collagenase digestion of adipose tissue. The release of adiponectin by non-fat cells (matrix+SV cells) was comparable to that by the adipocytes derived from the same amount of tissue while the adiponectin mRNA content of the pooled matrix and SV cell fractions was 40% of that in intact tissue. The adiponectin mRNA content was 48-fold greater in isolated adipocytes than in non-fat cells derived from adipose tissue. In contrast, the amount of adiponectin mRNA in vitro differentiated omental adipocytes was 1 x l0(6)-fold greater than that in cultured preadipocytes while that of leptin was 3 x 10(4)-fold greater. CONCLUSION: Adiponectin mRNA is present in the non-fat cells of freshly isolated adipose tissue and release by the non-fat cells derived from a gram of adipose tissue is comparable to that by adipocytes isolated from the same amount of tissue. While leptin is only released by mature adipocytes, adiponectin is released by both the non-fat cells and the fat cells derived from human omental adipose tissue.

Identification of omentin mRNA in human epicardial adipose tissue: comparison to omentin in subcutaneous, internal mammary artery periadventitial and visceral abdominal depots.

OBJECTIVE: The purpose of this study was to determine the relative distribution of omentin and visfatin mRNA in human epicardial, peri-internal mammary, upper thoracic, upper abdominal and leg vein subcutaneous adipose tissue as well as the distribution of omentin in the nonfat cells and adipocytes of human omental adipose tissue. BACKGROUND: Omentin is found in human omentum but not subcutaneous fat. Omentin and visfatin are considered markers of visceral abdominal fat. RESEARCH DESIGN AND METHODS: The mRNA content of omentin and visfatin was measured by qRT-PCR analysis of fat samples removed from humans undergoing cardiac or bariatric surgery. RESULTS: Omentin mRNA in internal mammary fat was 3.5%, that in the upper thoracic subcutaneous fat was 4.7% while that in the other subcutaneous fat depots was less than 1% of omentin in epicardial fat. The distribution of visfatin mRNA did not vary between the five depots. Omentin mRNA was preferentially expressed in the nonfat cells of omental adipose tissue since the omentin mRNA content of isolated adipocytes was 9% of that in nonfat cells, and similar results were seen for visfatin. The amount of omentin mRNA in differentiated adipocytes was 0.3% and that of visfatin 4% of that in nonfat cells. The amount of omentin mRNA in preadipocytes was virtually undetectable while that of visfatin was 3% of that in freshly isolated nonfat cells from omental adipose tissue. CONCLUSION: Omentin mRNA is predominantly found in epicardial and omental human fat whereas visfatin mRNA is found to the same extent in epicardial, subcutaneous and omental fat.

Predicting anti-HIV-1 activity of 6-arylbenzonitriles: computational approach using superaugmented eccentric connectivity topochemical indices.

Highly discriminating adjacency-cum-distance based topochemical indices termed as superaugmented eccentric connectivity topochemical indices for quantitative structure-activity and structure-property relationships (QSAR/QSPR) have been conceptualized in the present study. These indices were found to exhibit high sensitivity towards the presence and relative position of heteroatom(s), exceptionally high discriminating power and negligible degeneracy for all possible structures of five vertices containing one heteroatom. Utility of these indices was investigated for development of models for prediction of anti-human immunodeficiency virus (HIV)-1 activity using a data set comprising 81 differently substituted 6-arylbenzonitriles. The values of the superaugmented eccentric connectivity topochemical indices of all the analogues comprising the data set were computed using an in-house computer program. The resultant data was analyzed and suitable models were developed after identification of the active ranges. Subsequently, a biological activity was assigned to each analogue using these models which was then compared with the reported anti-HIV-1 activity. The accuracy of prediction was found to be approximately 81% for all the three topochemical models. High sensitivity towards presence and relative position of heteroatom(s), exceptionally high discriminating power amalgamated with low degeneracy offer proposed topochemical indices vast potential for isomer discrimination, similarity/dissimilarity, drug design, quantitative structure-activity/structure-property relationships, lead optimization and combinatorial library design.

Adduction of amiloride hydrochloride in urea through a modified technique for the dissolution enhancement.

Amiloride hydrochloride is a potassium-sparing diuretic since it favors sodium excretion and potassium reabsorption. In the present study, urea, a well-known adductor for linear compounds was successfully employed for inclusion of amiloride hydrochloride-a substituted cyclic organic compound through a modified technique. Formation of urea inclusion compounds was confirmed by FTIR, DSC and XRD. The minimum amount of rapidly adductible endocyte (RAE) required for adduction of amiloride hydrochloride in urea was estimated by a modified Zimmerschied calorimetric method. Urea-AH-RAE inclusion compounds containing varying proportions of guests were prepared and their thermal behavior studied by DSC. The inclusion compounds were also found to exhibit high content uniformity and markedly improved dissolution profile as demonstrated by increased dissolution efficiency. Studies reveal the possibility of exploiting co-inclusion of the drug in urea host lattice for the dissolution enhancement.

Minimally invasive surgery fellows would perform a wider variety of cases in their "ideal" fellowship.

BACKGROUND: With the increase in minimally invasive surgery (MIS) fellowships, the concept of the ideal and standardized training curriculum is emerging in importance. The authors hypothesize that the procedure mix in current MIS training is different from what current MIS fellows would expect for their "ideal" fellowship. METHODS: An anonymous survey of current MIS fellows examined their perceptions of the case diversity and volume they expect to perform in their fellowships as compared with an ideal fellowship. Differences between expected and ideal case volume were analyzed using Wilcoxon tests. RESULTS: A total of 32 questionnaires were returned. Current MIS fellows believe their expected training will exceed the ideal volume of laparoscopic cholecystectomies (p = 0.002). They believe their expected training is equivalent to ideal training in laparoscopic gastric bypass, ventral herniorraphy, inguinal herniorraphy, antireflux procedures, appendectomy, and diagnostic endoscopy (nonsignificant difference). However, current expected training falls short of their "ideal" case volume in laparoscopic gastric banding, colectomy, common bile duct exploration, gastrectomy, esophagectomy, splenectomy, adrenalectomy, hepatectomy, nephrectomy, and pancreatectomy (p < 0.05). The current MIS fellows also expect that their thoracoscopic, therapeutic endoscopy, and robotic procedure volume will be less than "ideal" (p < 0.05). CONCLUSION: In 13 of 20 procedure types, current MIS fellows expect to perform a smaller case volume than in an "ideal" fellowship. The ideal case volume in the MIS fellowship curriculum needs to be defined better.

Urea co-inclusion compounds of 13 cis-retinoic acid for simultaneous improvement of dissolution profile, photostability and safe handling characteristics.

13-cis Retinoic acid (cis-RA), a synthetic retinoid used in the treatment of severe acne, is known to exhibit extremely low aqueous solubility and high photosensitivity. In this study, urea, a well-known adductor for linear compounds, was successfully employed for the adduction of cis-RA - a substituted cyclic organic compound. Formation of urea inclusion compounds was confirmed by FTIR, DSC and XRD. A modified Zimmerschied calorimetric method was employed for the estimation of the minimum amount of rapidly adductible endocyte (RAE) required for adduction of cis-RA in urea. Urea-cis-RA-RAE inclusion compounds containing varying proportions of guests were prepared and their thermal behaviour studied by DSC. The inclusion compounds were found to have an improved dissolution profile as demonstrated by an overall increase in the dissolution efficiency. An accelerated photostability study, conducted as per Q1B ICH guidelines, revealed that co-inclusion of cis-RA in urea delayed photo-degradation of the drug when compared with that of the pure drug. The results suggest the possibility of exploiting co-inclusion of the drug in a urea host lattice for improved solubility, stability and reduced handling problems for cis-RA.

Prospective randomized controlled trial of laparoscopic trainers for basic laparoscopic skills acquisition.

BACKGROUND: Laparoscopic surgery requires a different set of skills than traditional open surgery. The acquisition of basic laparoscopic skills may help novices when learning laparoscopic procedures. This study tested the hypothesis that the combination of virtual reality and box trainers leads to better basic laparoscopic skill acquisition than either method alone or no training. METHODS: A randomized control trial involving preclinical medical students with no prior operative experience was performed. The students were grouped according to four training methods: virtual reality training, inanimate box training, a combination of both, and no training (control). The pre- and posttraining scores for four skills in the porcine laboratory were the metrics chosen for this study. RESULTS: A total of 65 students participated in this study. There were no differences among any of the pretraining scores (p > 0.05). The posttraining times differed between the four groups. Post hoc analyses showed statistically significant differences (p < 0.05) between the participants trained with both trainers and the control subjects. CONCLUSIONS: Our data demonstrate that the combination of virtual reality training and inanimate box training leads to better laparoscopic skill acquisition than either training method alone or no training at all. Optimal preclinical laparoscopic training should incorporate both virtual reality trainers and inanimate box trainers.

Predictive value of upper gastrointestinal studies versus clinical signs for gastrointestinal leaks after laparoscopic gastric bypass.

BACKGROUND: The utility of routine upper gastrointestinal (UGI) studies after laparoscopic Roux-en-Y gastric bypass (LRYGB) is a matter of great debate. Because the morbidity and mortality rates associated with an unrecognized postoperative leak are high after LRYGB, diagnosis of a postoperative leak earlier would be of benefit. Clinical signs, however, may predict the diagnosis of a postoperative leak more often. This study explored the hypothesis that UGI studies are more predictive than clinical signs for the early diagnosis of a postoperative leak after LRYGB. METHODS: All patients who underwent LRYGB at the authors' institution were included in this study. Charts were reviewed to examine immediate clinical signs (heart rate, temperature, and white blood cell count within the first 24 h), UGI studies, and clinical course. Sensitivity, specificity, positive predictive value, negative predictive value, and efficiency of clinical signs and UGI studies were calculated. RESULTS: This study included 245 patients with a 3% rate of leak. The positive and negative predictive value of UGI studies were 67% and 99%, respectively. Only an elevated white blood count had a better predictive value (100% for negative predictive value). The efficiency of UGI studies (98%) was better than that of heart rate (83%), white blood count (8%), or temperature (95%). CONCLUSIONS: According to our data, UGI studies are the most predictive of an early leak diagnosis. Clinical signs alone may not be as useful in predicting leaks early after laparoscopic gastric bypasses. Routine early postoperative UGI studies are a reasonable approach to predicting leaks after LRYGB.

Unexpected pathology during laparoscopic bariatric surgery.

BACKGROUND: The popularity of bariatric surgery has increased in recent years with the escalating incidence of morbid obesity in our society. The improvement in minimally invasive technology and the increased number of laparoscopic bariatric procedures being performed have resulted in the discovery of unexpected pathology not suspected preoperatively. The authors hypothesized that the occurrence of unexpected pathology is not associated with immediate adverse outcomes during laparoscopic bariatric procedures. METHODS: From December 2002 to June 2004, 398 patients underwent laparoscopic bariatric surgery for morbid obesity. A retrospective chart review was performed to determine the incidence of unexpected findings and their effect on patient results. RESULTS: Nine unexpected pathologic lesions were found in eight patients (2%). The findings included lesions on the small bowel (n = 3), stomach (n = 4), and liver (n = 2). In all cases except one (for which a biopsy was performed), the abnormalities were found and removed laparoscopically. The final pathology showed gastric leiomyomas (n = 2), gastric gastrointestinal stromal cell tumors (n = 2), ectopic pancreatic tissue (n = 2), arteriovenous malformation (n = 1), biliary adenoma (n = 1), and fibrosed hemangioma (n = 1). The planned bariatric procedures were completed for all the patients without incident. No complications occurred postoperatively, and all were discharged in 1 to 3 days (mean, 2 days). CONCLUSIONS: Unexpected findings occur with relative frequency during laparoscopic bariatric procedures. Biopsy or removal of these lesions usually does not increase complications nor preclude continuation of the planned bariatric procedure.

Establishing a laparoscopic bariatric program in a safety net hospital.

BACKGROUND: Most laparoscopic bariatric programs are situated in a community- or university-based hospital. The authors have recently initiated a program at a safety net hospital. This investigation hypothesizes that a laparoscopic bariatric program can be established at a safety net hospital with good clinical and financial results. METHODS: A laparoscopic bariatric program was initiated December 2002 at a safety net hospital. The program included a dedicated operative suite, an operative team, a bariatric unit, and a clinical pathway. The data for all the patients who underwent laparoscopic gastric bypasses up to June 2003 were analyzed. The patients were analyzed by type of insurance: government-sponsored insurance (G) or commercial insurance (C). RESULTS: There were 104 patients during this period. Their mean age was 40 years (range, 18-63 years), and their mean body mass index was 48 (range, 38-62). The median length of hospital stay was 2 days (mean, 3.9 days). Hypertension and diabetes were resolved for more than 80% of the patients. The average percentage of excess body weight loss was 73% after 1 year. There were no significant clinical differences between payor groups. The payor mix was 31% G and 69% C. The mean collection rates for hospital charges were 10% for G versus 53% for C (p < 0.0001). CONCLUSIONS: A laparoscopic bariatric program can be established in a safety net hospital with good clinical results. Findings showed that 1-year weight loss and comorbidity improvement/resolution compares favorably with those of other programs. Despite the overall poor payor mix of many safety net hospitals, a bariatric program can be established and can attract a high rate of commercially insured patients.

A research agenda for gastrointestinal and endoscopic surgery.

BACKGROUND: Development of a research agenda may help to inform researchers and research-granting agencies about the key research gaps in an area of research and clinical care. The authors sought to develop a list of research questions for which further research was likely to have a major impact on clinical care in the area of gastrointestinal and endoscopic surgery. METHODS: A formal group process was used to conduct an iterative, anonymous Web-based survey of an expert panel including the general membership of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES). In round 1, research questions were solicited, which were categorized, collapsed, and rewritten in a common format. In round 2, the expert panel rated all the questions using a priority scale ranging from 1 (lowest) to 5 (highest). In round 3, the panel re-rated the 40 questions with the highest mean priority score in round 2. RESULTS: A total of 241 respondents to round 1 submitted 382 questions, which were reduced by a review panel to 106 unique questions encompassing 33 topics in gastrointestinal and endoscopic surgery. In the two successive rounds, respectively, 397 and 385 respondents ranked the questions by priority, then re-ranked the 40 questions with the highest mean priority score. High-priority questions related to antireflux surgery, the oncologic and immune effects of minimally invasive surgery, and morbid obesity. The question with the highest mean priority ranking was: "What is the best treatment (antireflux surgery, endoluminal therapy, or medication) for GERD?" The second highest-ranked question was: "Does minimally invasive surgery improve oncologic outcomes as compared with open surgery?" Other questions covered a broad range of research areas including clinical research, basic science research, education and evaluation, outcomes measurement, and health technology assessment. CONCLUSIONS: An iterative, anonymous group survey process was used to develop a research agenda for gastrointestinal and endoscopic surgery consisting of the 40 most important research questions in the field. This research agenda can be used by researchers and research-granting agencies to focus research activity in the areas most likely to have an impact on clinical care, and to appraise the relevance of scientific contributions.

Urea inclusion compounds of enalapril maleate for the improvement of pharmaceutical characteristics.

Urea is a well known adductor for linear organic compounds. In the present study, enalapril maleate, a substituted cyclic organic compound, was successfully included in urea together with a suitable rapidly adductible endocyte (RAE). Formation of the urea inclusion compound was confirmed by Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction. The modified Zimmerschied calorimetric method was used to estimate the minimum amount of RAE required for adduction of enalapril maleate in urea. Urea-enalapril maleate-RAE inclusion compounds containing varying proportions of guests were prepared and their thermal behaviour studied by differential scanning calorimetry. Regression analysis revealed an excellent r(2) value with regard to the influence of the relative proportion of RAE on the heat of decomposition. The inclusion compounds were found to exhibit good content uniformity and improved dissolution profile as demonstrated by increased dissolution efficiency. Studies revealed that urea inclusion may be a promising alternative for the formulation of potent poorly soluble drugs into immediate release products.

Solid dispersion adsorbates for enhancement of dissolution rates of drugs.

Amalgamation of solid dispersion and melt adsorption technologies was utilized for enhancing the dissolution rate of poorly soluble drugs. Glibenclamide was employed as a model drug. PEG6000 and Gelucire44/14 were used as hydrophilic carriers for the preparation of solid dispersions, and lactose was utilized as an adsorbent for the preparation of solid dispersion adsorbates. A high dissolution rate of solid dispersion adsorbates was observed when compared to solid dispersions alone and one of the marketed products.

Topochemical models for the prediction of permeability through blood-brain barrier.

Relationship between the topochemical indices and permeability of diverse series of compounds through blood-brain barrier has been investigated. Three-topochemical indices, Wiener's topochemical index--a distance-based topochemical descriptor, molecular connectivity topochemical index--an adjacency based topochemical descriptor and eccentric connectivity topochemical index--an adjacency-cum-distance based topochemical descriptor, were used for the present investigation. A data set comprising of 28 compounds with established CNS permeation tendency was selected for present study. The values of all the three-topochemical indices in the original as well as in the normalized form for each of the 28 compounds comprising the data set were computed using an in-house computer program. Resultant data was analyzed and suitable models were developed after identification of the permeable ranges. Subsequently, permeability characteristic was assigned to each compound involved in the data set using these models, which was then compared with the reported permeability through blood-brain barrier. Accuracy of prediction was found to vary from a minimum of 83% to a maximum of approximately 95% using these models.

Immunolocalization of fibroblast growth factor-2 (FGF-2) in the developing root and supporting structures of the murine tooth.

Epithelio-mesenchymal interactions are active during the development of the root of the tooth and are regulated by a variety of growth factors, such as fibroblast growth factors. FGF-2, 3, 4, and 8 have all been shown to play a role in the development of the crown of the tooth, but less is known about the factors that govern root formation, particularly FGF-2. The aim of this study was thus to elucidate the spatial and temporal expression of FGF-2 in the root of the developing tooth, as this growth factor is believed to be a mediator of epithelio-mesenchymal interactions. Parasagittal sections of the maxillary and mandibular arches of post-natal mice were utilized and the roots of the molar teeth were studied. Immunocytochemistry utilizing an antibody to FGF-2 was performed on sections of teeth at various stages of development. Intense immunostaining for FGF-2 was observed in differentiating odontoblasts at the apical end of the tooth and in the furcation zone of the developing root at all the stages examined. FGF-2 localization was also observed in cementoblasts on post-natal days 16, 20 and 24. The pattern of localization of FGF-2 in the developing root suggests that this growth factor may participate in the signaling network associated with root development.