Salivary Menopausal Markers and Oral Health Status - A Hidden Hook Up.

Aim and Objectives: The aim of our study was to evaluate salivary estradiol and salivary calcium in postmenopausal women with varying degrees of oral dryness. The primary objective was to establish the interrelationship between salivary parameters and oral health status among menopausal women and compare the same with premenopausal women and normal controls. Materials and Methods: The study included 60 women Group I consisted of healthy menstruating women between 25 and 34 years of age. In Group II premenopausal women between 35 and 45 years of age were present and Group III consisted of menopausal women between 45 and 60 years of age. Unstimulated saliva was collected from the participants and estradiol analysis was done using ELISA method and calcium analysis was done using Arsenazo III reaction using colorimetric method. The oral health status in these patients was determined by using xerostomia score, Russell's periodontal score, and oral hygiene index. The values obtained were subjected to statistical analysis and the results were derived. Results: On oral examination, most of them had poor oral hygiene, periodontal disease, and moderate to severe levels of xerostomia. Salivary estradiol levels were low and salivary calcium levels were high among postmenopausal women and as salivary estradiol levels decreased there was an increase in xerostomia scores and salivary calcium. And also as salivary calcium levels increased the periodontal disease scores increased. All parameters were within normal limits among healthy menstruating women. Conclusion: Saliva can be a preferred medium and an emerging alternative for serum to estimate estradiol and calcium levels. As a dentist, we have to educate them about the oral changes they will experience during menopause and emphasize its strong association between low estradiol levels. Oral hygiene instructions should be given for the maintenance of healthy periodontium. Menopausal women who experience severe postmenopausal symptoms can be identified and the dentist and gynecologist can work hand in hand to treat the symptoms of these women.

A Novel Hybrid Feature Extraction Model for Classification on Pulmonary Nodules

In this paper an improved Computer Aided Design system can offer a second opinion to radiologists on early diagnosis of pulmonary nodules on CT (Computer Tomography) images. A Deep Convolutional Neural Network (DCNN) method is used for feature extraction and hybridize as combination of Convolutional Neural Network (CNN), Histogram of Oriented Gradient (HOG), Extended Histogram of Oriented Gradients (ExHOG) and Local Binary Pattern (LBP). A combination of shape, texture, scaling, rotation, translation features extracted using HOG, LBP and CNN. The Homogeneous descriptors used to extract the feature of lung images from Lung Image Database Consortium (LIDC) are given to classifiers Support Vector Machine (SVM), K-Nearest Neighbour (KNN), Decision Tree and Random Forest to classify nodules and non-nodules. Experimental results demonstrate the effectiveness of the proposed method in terms of accuracy which gives best result than the competing methods.

Accuracy of estimation of dental age in comparison with chronological age in Indian population--a comparative analysis of two formulas.

UNLABELLED: Demirjian's 8-teeth method widens the assessment in a wider age group, in comparison with the original 7-teeth method. AIM AND OBJECTIVE: Evaluate age in children, adolescents and young adults using Demirjian's 8-Teeth Method in an Indian population. Compare the effectiveness of existing Demirjian's formula with that of the Indian formula. MATERIALS AND METHOD: Panoramic radiographs of 50 male and 50 female patients aged between 5 and 24 years were collected. The radiographs were interpreted using Demirjian's 8-teeth method and the dental age calculated using Demirjian's formula and the Indian formula. Both the formula's were compared using paired 't' test (SPSS Statistics 11.5). RESULTS: Among the 100 samples the mean chronological age in 50 males was 13.44 years and mean chronological age in 50 females was 13.12 years. By using Demirjian's formula the mean dental age in male was 11.81 years and that in female was 11.58 years. By using Indian Formula the mean dental age in male was 13.54 years and that in female was 14.06 years. The mean dental age by both the formulas were compared with the corresponding chronological age. It was evaluated that the Demirjian's formula underestimated the mean dental age by 1.63 years in males and by 1.54 years in females, whereas a variation of 0.10 years in male and 0.94 years in female was found with the Indian formula. The mean dental age obtained using Indian formula was approximating with the chronological age in the male and female by a margin of 0.94 years. CONCLUSION: Acharya's Indian formula is more effective in evaluating the dental age closer to the chronological age of an individual in an Indian population in comparison with the existing Demirjian's formula.

A fluorescence-based screening assay for DNA damage induced by genotoxic industrial chemicals.

A rapid screening assay to detect chemically-induced DNA damage resulting from exposure of surrogate DNA to genotoxic compounds is reported. This assay is based on changes in the melting and annealing behavior observed for damaged DNA. Exposure of calf thymus DNA to genotoxic industrial chemicals reduced the extent to which the DNA annealed as measured using a double strand DNA selective fluorescent indicator dye. Formaldehyde, acrolein, crotonaldehyde and bromoethane showed the most prominent effects, chloroacetone and allylamine exhibited lesser effects, and acryrlonitrile showed no statistically significant assay response. The assay response for formaldehyde and crotonaldehyde were measured over the concentration range of 10-100 mM and 50-300 mM, respectively. This assay showed little response for the cytotoxic compounds phenol, cyclohexane and toluene but was sensitive to the effects of DNA damaging compounds such as mitomycin C and glutaraldehyde.

Chemotherapeutic activity of clofazimine and its analogues against Mycobacterium tuberculosis. In vitro, intracellular, and in vivo studies.

Clofazimine (CFM), a riminophenazine drug, is primarily used in therapy for leprosy and Mycobacterium avium infections. With an objective of identifying drugs active against Mycobacterium tuberculosis, including those with multi-drug resistance, we investigated CFM and nine of its chemical analogues. Among these, B746 and B4101 had better activity than CFM against six drug-susceptible and nine single/multiple drug-resistant M. tuberculosis strains. B746 also showed slightly better activity than CFM against intracellular M. tuberculosis in J774A.1 macrophages and was comparable to CFM in its in vivo activity against experimental tuberculosis in C57BL/6 mice. Interestingly, it caused less pigmentation in internal organs.

Maintenance of therapeutically active levels of isoniazid for prolonged periods in rabbits after a single implant of biodegradable polymer.

SETTING: Poor patient compliance is the serious limiting factor in the chemotherapy of tuberculosis. OBJECTIVE: To solve this problem we have been developing depot-drug delivery of antimycobacterial drugs. Earlier studies with mice using isoniazid in polylactic-co-glycolic acid (PLGA) co-polymer have shown that a single implant of the polymer could ensure sustained levels of free isoniazid for up to 8 weeks. Similar studies were not undertaken in rabbits. DESIGN: The biodegradable PLGA polymer rods containing isoniazid were implanted on the back of the rabbits under anaesthesia in an isoniazid dose of 90 mg/kg. Concentrations of isoniazid and acetylisoniazid in serum and urine were determined by the high-performance liquid chromatography (HPLC) method at close intervals up to 96 h to study the burst-size, and later at weekly intervals up to 9 weeks to study the sustained levels. RESULTS AND CONCLUSIONS: There was no abnormal release of isoniazid in the earlier periods. Concentrations of isoniazid > or = 0.2 microgram/ml were found both in serum and urine up to 63 days after implant. Urine specimen obtained at 6 weeks after giving the implant inhibited the growth of Mycobacterium tuberculosis in vitro as measured by the radiometric (Bactec) method. These findings in non-rodent animal species confirm the usefulness of the depot-drug delivery method of drug administration and warrant hopes for the successful treatment of tuberculosis avoiding the problem of non-compliance.

Bioavailability and chemotherapeutic activity of clofazimine against Mycobacterium avium complex infections in beige mice following a single implant of a biodegradable polymer.

We have studied the bioavailability of clofazimine following administration of a single dose of the drug in the biodegradable polymer polylactic-co-glycolic acid (PLGA). We compared the levels of clofazimine achieved in the liver with single implants with those obtained with daily oral treatment. Even though the levels achieved with implants were much lower than those obtained after daily oral treatment, they were higher than the MIC of clofazimine for Mycobacterium leprae, Mycobacterium tuberculosis and Mycobacterium avium complex (MAC). Experimental studies in beige mice after infection with MAC strain 101 showed similar reductions in cfu counts, after both single dose polymer and daily oral treatment. Macroscopically, hyperpigmentation giving an orange-yellow colour to all visceral organs, was seen in animals after daily oral treatment but not in those animals that received polymer implants.

Experimental chemotherapy of tuberculosis using single dose treatment with isoniazid in biodegradable polymers.

In previous studies we showed that a single implant of polylactic-co-glycolic acid (PLGA) polymer as a film containing isoniazid ensured sustained release of the drug for up to 4 weeks. These studies have been extended to PLGA polymer as a rod which is retrievable. Both types of implant gave therapeutically active levels of free isoniazid in liver and urine for prolonged periods. We assessed the in vivo chemotherapeutic efficacy of the rod implant against heavy infections of virulent Mycobacterium tuberculosis in C57Bl/6 mice. The chemotherapeutic data essentially confirmed the bioavailability data. In one chemotherapeutic study, one (7%) out of 15 mice which received the isoniazid polymer implant died within 30 days of bacterial challenge, while none of those receiving daily oral treatment died. In contrast, 14 (93%) of the 15 control mice died during the same period. In a second study similar results were obtained.

Classification of children as slow or rapid acetylators based on concentrations of isoniazid in saliva following oral administration of body-weight and surface-area-related dosages of the drug.

The acetylator phenotype of 180 children aged 3-11 years was determined on the basis of isoniazid concentrations in saliva collected at 5 hours after oral administration of body-weight and surface-area-related dosages of the drug in a syrup form. Isoniazid 2.5 mg/kg was administered on one occasion and 75 mg/m2 surface-area on another, with an interval of 3 days between the occasions. A cross-over design was employed and the sequence was determined by random allocation. The distribution of the concentrations was bimodal with both procedures, indicating the presence of two groups namely, the slow and rapid acetylators. The criterion for a rapid acetylator was a concentration of 0.3 micrograms/ml or less by body-weight-related dosage and 0.4 micrograms/ml or less by that based on surface-area. Based on these criteria, 62% of the children were classified as slow acetylators and 38% as rapid acetylators by body-weight, and 59 and 41%, respectively by surface-area, and the findings were similar in children in the different age-groups. The agreement between the two procedures was 98%.

Rifampin-induced release of hydrazine from isoniazid. A possible cause of hepatitis during treatment of tuberculosis with regimens containing isoniazid and rifampin.

The effect of daily administration of rifampin on the direct conversion of isoniazid to isonicotinic acid and hydrazine by isoniazid hydrolase was investigated in 6 slow and 8 rapid acetylators of isoniazid. The proportion of isoniazid metabolized through this direct pathway during the first 6 h was estimated from the ratio of total isonicotinic acid formed to acetylisoniazid in urine after administration of isoniazid or acetylisoniazid. In slow acetylators, this proportion was approximately 3% when isoniazid alone was administered and approximately 6% during the maximal phase of induction caused by the daily administration of rifampin in addition to isoniazid (p less than 0.001); in rapid acetylators, the proportions were considerably less (less than 1 and 2.5%, respectively), suggesting that isoniazid hydrolase was induced by rifampin. The increased formation of hydrazine, a known hepatotoxic agent in animals, could explain the substantially higher frequency of the occurrence of hepatitis in slow than in rapid acetylators among tuberculous patients treated with daily rifampin and isoniazid.

Effect of prednisolone and rifampin on isoniazid metabolism in slow and rapid inactivators of isoniazid.

The effect of prednisolone and rifampin, alone and in combination, on the biodisposition of isoniazid in slow and rapid inactivators of isoniazid was investigated. In one investigation, we made serial determinations of plasma isoniazid concentrations up to 8 h and of isoniazid and acetylisoniazid in excreted urine up to 8.5 h in patients receiving isoniazid alone on one occasion and isoniazid plus prednisolone or isoniazid plus rifampin on another. Prednisolone caused a significant decrease in the plasma isoniazid concentrations in both slow and rapid inactivators. It also enhanced the renal clearance of isoniazid in both slow and rapid inactivators and increased the rate of acetylation of isoniazid in slow inactivators only. Rifampin had no effect on the biodisposition of isoniazid in either slow or rapid inactivators. In a second investigation, one group of slow and rapid inactivators received isoniazid and rifampin, and a different group received prednisolone, in addition. Plasma isoniazid concentrations in slow inactivators receiving prednisolone were significantly lower than in those who received isoniazid and rifampin only. In rapid inactivators, plasma isoniazid concentrations were similar in the two groups of patients, suggesting that concomitant administration of rifampin had considerably modified the prednisolone effect on the biodisposition of isoniazid in these patients.

Studies of serial plasma Isoniazid concentrations with different doses of a slow-release preparation of Isoniazid.

The suitability of a slow-release matrix preparation of isoniazid for use in once-weekly chemotherapy has been investigated in South Indian patients. Serial plasma isoniazid concentrations were determined up to 6 hours following doses of 15, 30, 45 and 60 mg/kg body-weight in rapid inactivators and up to 10 hours following doses of 15, 30 and 45 mg/kg in slow inactivators. The isoniazid levels were sustained, and the peak concentrations (per unit dose) were considerably lower than with ordinary isoniazid. It was estimated that a matrix isoniazid dose of 35 mg/kg in slow inactivators and 50 mg/kg in rapid inactivators would produce a peak similar to that attained with a non-toxic dose or ordinary isoniazid 15 mg/kg in slow inactivators. A second investigation showed that matrix isoniazid 40 mg/kg in rapid inactivators produced a coverage (with 0.2 mug/ml) and exposure similar to those attained in slow inactivators with a highly effective dose of ordinary isoniazid 15 mg/kg, while 30 mg/kg gave substantially lower values. In both investigations, disproportionately large increases in plasma isoniazid concentrations were observed in rapid inactivators with an increase in the matrix isoniazid dose. In slow inactivators, both doses of matrix isoniazid, 30 and 40 mg/gk, resulted in coverage and exposure that were substantially higher than those obtained with ordinary isoniazid 15 mg/kg.

Inactivation of isoniazid by condensation in a syrup preparation.

This paper reports the gross and rapid condensation of isoniazid in a commercial black-currant-flavoured syrup. In vitro studies showed that the condensation was due, at least partly, to the glucose contained in the syrup, paper chromatography having demonstrated the presence of D(+)-glucose isonicotinoyl hydrazone. Controlled studies in human beings showed that the absorption of isoniazid from the preparation was considerably impaired by this condensation.It is concluded that sugars such as glucose, fructose, and sucrose-especially glucose-should not be used in isoniazid syrup preparations, and it is suggested that sorbitol, a stable non-carbonyl compound, might be a suitable substitute.