An Alternative Approach to Tablet Splitting and Grinding for Medication Administration.

Tablet formulations fail to meet the needs of patients unable to swallow tablets such as pediatric, elderly, and patients that must receive medications via feeding tubes. Our objective was to develop and test a new, simple device (XTEMP-R) and the methodology for converting tablets into a homogeneous suspension for medication administration. We developed a new device comprised of a flexible receptacle, a tight-fitting cap, and a suction cup bottom to convert tablets into liquid preparations. Tuberculosis treatment drugs, TBAJ-876 and TBI-223, were dispersed within the device utilizing water and commonly available suspending vehicles. We investigated the effectiveness of the XTEMP-R device in dispersing tablets. This was accomplished by visual observations, determining the fineness of dispersion, and measuring the total drug recovery from the dispersions in XTEMP-R. We investigated the accuracy and reproducibility of delivering aliquots from these suspensions by determining the dose reproducibility upon suspension and upon redispersion after 24 hours. The effectiveness of the device was also evaluated using commercially available tablets of acetaminophen, amlodipine, glimepiride, metformin, and valsartan. The suspensions were visually uniform without any large particles. The suspensions passed through a #18 sieve confirming that the particles were less than 1000 µm. The average total dose recovery of three suspensions each was determined to be 101.3% and 99.2% for TBI-223 and TBAJ-876, respectively. Reproducibility from aliquots of 2 mL each was 98.9% to 99.7% for three replicates of TBI-223 suspensions, and 102.6% to 103.2% for TBAJ-876 suspensions. Aliquots tested after 24 hours confirmed uniform redispersibility. We have demonstrated that XTEMP-R can be utilized to prepare homogeneous suspensions conveniently and efficiently in less than 10 minutes without any drug loss. Aliquots for partial dose delivery can be withdrawn accurately. These findings demonstrate that XTEMP-R can be used to accurately deliver doses of suspensions for patients who cannot swallow tablets.

Antimicrobial Use and Resistance in Surplus Dairy Calf Production Systems.

Surplus calves, which consist predominately of male calves born on dairy farms, are an underrecognized source of antimicrobial-resistant (AMR) pathogens. Current production systems for surplus calves have important risk factors for the dissemination of pathogens, including the high degree of commingling during auction and transportation and sometimes inadequate care early in life. These circumstances contribute to an increased risk of respiratory and other infectious diseases, resulting in higher antimicrobial use (AMU) and the development of AMR. Several studies have shown that surplus calves harbor AMR genes and pathogens that are resistant to critically important antimicrobials. This is a potential concern as the resistant pathogens and genes can be shared between animal, human and environmental microbiomes. Although knowledge of AMU and AMR has grown substantially in dairy and beef cattle systems, comparable studies in surplus calves have been mostly neglected in North America. Therefore, the overall goal of this narrative review is to summarize the existing literature regarding AMU and AMR in surplus dairy calf production, highlight the management practices contributing to the increased AMU and the resulting AMR, and discuss potential strategies and barriers for improved antimicrobial stewardship in surplus calf production systems.

1H nuclear magnetic resonance-based metabolite profiling of guava leaf extract: an attempt to develop a prototype for standardization of plant extracts.

BACKGROUND: Herbal medicines are fast gaining popularity. However, their acceptability by modern practitioners is low which is often due to lack of standardization. Several approaches towards standardization of herbals have been employed. The current study attempted to recognize key peaks from 1H NMR spectra which together would comprise of a spectral fingerprint relating to efficacy of Psidium guajava (guava) leaf extract as an antidiarrhoeal when a number of unidentified active principles are involved. METHODS: Ninety samples of guava leaves were collected from three locations over three seasons. Hydroalcoholic (water and ethanol, 50:50) extracts of these samples were prepared and their 1H NMR spectra were acquired. Spectra were also obtained for quercetin, ferulic acid and gallic acid as standards. Eight bioassays reflecting different stages of diarrhoeal pathogenesis were undertaken and based on pre-decided cut-offs, the extracts were classified as 'good' or 'poor' extracts. The bioactivity data was then correlated with the 1H NMR profiles using Regression or Orthogonal Partial Least Square-Discriminant Analysis (OPLS-DA). RESULTS: OPLS-DA showed seasonal and regional segregation of extracts. Significant models were established for seven bioassays, namely those for anti-bacterial activity against Shigella flexneri and Vibrio cholerae, adherence of E. coli, invasion of E. coli and S. flexneri and production and binding of toxin produced by V. cholerae. It was observed that none of the extracts were good or bad across all the bioassays. The spectral analysis showed multiple peaks correlating with a particular activity. Based on NMR and LC-MS/MS, it was noted that the extracts contained quercetin, ferulic acid and gallic acid. However, they did not correlate with the peaks that segregated extracts with good and poor activity. CONCLUSIONS: The current study identified key peaks in 1H NMR spectra contributing to the anti-diarrhoeal activity of guava leaf extracts. The approach of using spectral fingerprinting employed in the present study can thus be used as a prototype towards standardization of plant extracts with respect to efficacy.

Options for reducing HIV transmission related to the dead space in needles and syringes.

BACKGROUND: When shared by people who inject drugs, needles and syringes with different dead space may affect the probability of HIV and hepatitis C virus (HCV) transmission differently. METHODS: We measured dead space in 56 needle and syringe combinations obtained from needle and syringe programs across 17 countries in Europe and Asia. We also calculated the amounts of blood and HIV that would remain in different combinations following injection and rinsing. RESULTS: Syringe barrel capacities ranged from 0.5 to 20 mL. Needles ranged in length from 8 to 38 mm. The average dead space was 3 µL in low dead space syringes with permanently attached needles, 13 µL in high dead space syringes with low dead space needles, 45 µL in low dead space syringes with high dead space needles, and 99 µL in high dead space syringes with high dead space needles. Among low dead space designs, calculated volumes of blood and HIV viral burden were lowest for low dead space syringes with permanently attached needles and highest for low dead space syringes with high dead space needles. CONCLUSION: The dead space in different low dead space needle and syringe combinations varied substantially. To reduce HIV transmission related to syringe sharing, needle and syringe programs need to combine this knowledge with the needs of their clients.

Psidium guajava: A Single Plant for Multiple Health Problems of Rural Indian Population.

The rural population in India faces a number of health problems and often has to rely on local remedies. Psidium guajava Linn. (guava), a tropical plant which is used as food and medicine can be used by rural communities due to its several medicinal properties. A literature search was undertaken to gauge the rural health scenario in India and compile the available literature on guava so as to reflect its usage in the treatment of multiple health conditions prevalent in rural communities. Towards this, electronic databases such as Pubmed, Science Direct, google scholar were scanned. Information on clinical trials on guava was obtained from Cochrane Central Register of Controlled Trials and Clinicaltrial.gov. The literature survey revealed that guava possesses various medicinal properties which have been reported from across the globe in the form of ethnobotanical/ethnopharmacological surveys, laboratory investigations and clinical trials. Besides documenting the safety of guava, the available literature shows that guava is efficacious against the following conditions which rural communities would encounter. (a) Gastrointestinal infections; (b) Malaria; (c)Respiratory infections; (d) Oral/dental infections; (e) Skin infections; (f) Diabetes; (g) Cardiovascular/hypertension; (h) Cancer; (i) Malnutrition; (j) Women problems; (k) Pain; (l) Fever; (m) Liver problems; (n) Kidney problems. In addition, guava can also be useful for treatment of animals and explored for its commercial applications. In conclusion, popularization of guava, can have multiple applications for rural communities.

Electron beam irradiation revealed genetic differences in radio-sensitivity and generated mutants in groundnut (Arachis hypogaea L.).

Electron beam accelerators are being used for many industrial applications including food and agriculture. A 10MeV linear accelerator facility was standardized for low dose application 0.1-1 kGy) in pulse mode using unscanned scattered beam for irradiation of groundnut seeds for mutation breeding. Using this facility, 50% growth reduction (GR50) dose was standardized in five groundnut genotypes. There were significant differences for radio-sensitivity among these genotypes. Seed mutagenesis of two groundnut genotypes, TG 26 and TG 68 with electron beam has generated one large seeded and four high yielding mutants in preliminary field trials.

Adding value to antiretroviral proficiency testing.

BACKGROUND: Clinical trial specimens tested for antiretroviral (ARV) concentrations often require compliance with Clinical Laboratory Improvement Act and/or the Food and Drug Administration bioanalytical guidance. EXPERIMENTAL: The Clinical Pharmacology Quality Assurance Program (CPQA) designed 8 proficiency testing (PT) rounds over 4 years to assess precision, specificity and stability. RESULTS: Ten laboratories provided blinded proficiency data to support continued acceptable precision of ARV methods. Specificity samples identified little bias for individual methods; hemolyzed (87%) and lipemic (86%) results were ≤ 10% of their control results. Stability was established for ARVs in plasma at -70°C for 2.5-3.6 years. CONCLUSION: PT provided by the CPQA assured continued acceptability of individual laboratory assay performances for precision and specificity, and obtained ARV stability during long term storage.

Approaches in fostering quality parameters for medicinal botanicals in the Indian context.

India is among the important megabiodiversity centers of the world with nearly 45,000 known plant species. This diversity coupled with a rich heritage of traditional knowledge has made India a home to several important time-honored systems of health care such as Ayurveda, Siddha and Unani. Herbal medicines, however, are associated with a number of shortcomings including uniform efficacy and lack of appropriate quality control measures at various stages of product development. The review intends to outline the importance of fostering quality parameters towards standardization and manufacturing of botanicals for India to emerge as a leader in global market of herbal products. Literature survey was carried out on important parameters for processing and manufacturing of botanicals. The review highlights that there have been constant efforts for developing state of the art technologies in the field of herbal research. It also reflects that Government authorities have also taken a number of initiatives to formulate appropriate guidelines from standardization of raw materials to obtaining botanical products. However, in the Indian context, there exist certain lacunae in the current regulatory mechanisms which need to be strengthened and stringently implemented to ensure safety, purity and efficacy of herbal medicines. Towards this the approaches being developed globally can be adopted. Based on the literature reviewed, in our opinion, four areas viz., benefit sharing, investment by industry, standardization and national/international networking structure need immediate attention for strengthening Traditional Systems of Medicine in India.

Bactericidal Effect of Selected Antidiarrhoeal Medicinal Plants on Intracellular Heat-Stable Enterotoxin-Producing Escherichia coli.

Diarrhoeal diseases due to enterotoxigenic Escherichia coli continue to be a cause of global concern. Medicinal plants have been gaining popularity as promising antidiarrhoeal agents. In the present study, four antidiarrhoeal plants, viz. Aegle marmelos, Cyperus rotundus, Psidium guajava and Zingiber officinale were screened against a heat-stable toxin-producing enterotoxigenic E. coli strain. Decoctions of these plants were studied for their effect on intracellular killing of the bacterial strain using murine monocytic cell line, J774. [(3)H] thymidine release assay was used to evaluate the apoptotic/necrotic effect. All plants at concentrations <1% enhanced intracellular killing of the bacteria by J774 cells. However, at higher concentrations, the decoctions induced apoptosis in J774 cells. The study demonstrates that these plants could control diarrhoea caused by heat-stable toxin-producing enterotoxigenic E. coli through their immunomodulatory effect.

Clinical pharmacology quality assurance program: models for longitudinal analysis of antiretroviral proficiency testing for international laboratories.

Among National Institutes of Health HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals. Drug assay data are, in turn, entered into study-specific data sets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis, and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semiannual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1) assess the precision and accuracy of concentrations reported by individual CPLs and (2) determine factors associated with round-specific and long-term assay accuracy, precision, and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21) drug concentration results reported for clinical trial samples by multiple CPLs). Using the Clinical Laboratory Improvement Act acceptance of meeting criteria for ≥2/3 consecutive rounds, all 10 laboratories that participated in 3 or more rounds per analyte maintained Clinical Laboratory Improvement Act proficiency. Significant associations were present between magnitude of error and CPL (Kruskal-Wallis P < 0.001) and antiretroviral (Kruskal-Wallis P < 0.001).

Use of SPME-HS-GC-MS for the analysis of herbal products containing synthetic cannabinoids.

The increasing prevalence and use of herbal mixtures containing synthetic cannabinoids presents a growing public health concern and legal challenge for society. In contrast to the plant-derived cannabinoids in medical marijuana and other cannabinoid-based therapeutics, the commonly encountered synthetic cannabinoids in these mendaciously labeled products constitute a structurally diverse set of compounds of relatively unknown pharmacology and toxicology. Indeed, the use of these substances has been associated with an alarming number of hospitalizations and emergency room visits. Moreover, there are already several hundred known cannabinoid agonist compounds that could potentially be used for illicit purposes, posing an additional challenge for public health professionals and law enforcement efforts, which often require the detection and identification of the active ingredients for effective treatment or prosecution. A solid-phase microextraction headspace gas chromatography-mass spectrometry method is shown here to allow for rapid and reliable detection and structural identification of many of the synthetic cannabinoid compounds that are currently or could potentially be used in herbal smoking mixtures. This approach provides accelerated analysis and results that distinguish between structural analogs within several classes of cannabinoid compounds, including positional isomers. The analytical results confirm the continued manufacture and distribution of herbal materials with synthetic cannabinoids and provide insight into the manipulation of these products to avoid legal constraints and prosecution.

Studies on the activity of Cyperus rotundus Linn. tubers against infectious diarrhea.

To study the antidiarrheal activity of the decoction of Cyperus rotundus Linn. tubers using representative assays of diarrheal pathogenesis and understand its mechanism of action.Antibacterial, antigiardial and antirotaviral activities were studied. Effect on adherence of enteropathogenic Escherichia coli (EPEC) and invasion of enteroinvasive E. coli (EIEC) and Shigella flexneri to HEp-2 cells was evaluated as a measure of effect on colonization. Effect on enterotoxins such as enterotoxigenic E. coli (ETEC) heat labile toxin (LT), heat stable toxin (ST) and cholera toxin (CT) was also assessed. The decoction showed antigiardial activity, reduced bacterial adherence to and invasion of HEp-2 cells and affected production of CT and action of LT. The decoction of C. rotundus does not have marked antimicrobial activity and exerts its antidiarrheal action by mechanisms other than direct killing of the pathogen.

Relation between central corneal thickness and intraocular pressure in Punjabi population.

OBJECTIVE: The motive of this study was to determine the variation of central corneal thickness (CCT) in the Punjabi population and to examine its relationship with intraocular pressure (IOP) using a non-contact tonometer. The study and results emphasize the effects of age, sex and refraction on this relationship, which is important for the diagnosis and prevention of glaucoma in adequate time. METHODS: The study design was a cross-sectional, population-based survey. The participants were 279 females and 253 males of Punjab Province, India, in the age group of 21-70 years. The CCT was measured using an ultrasonic pachymeter, and the IOP was measured using an air-puff tonometer in all subjects. RESULTS: The mean values of CCT and IOP were observed to vary imprecisely with age. The measurement of both parameters was also affected by sex and refraction. The linear regression analysis suggests that the mean value of CCT grows progressively with increasing value of mean IOP. A significant positive correlation was identified between CCT and IOP in the age group of 21-70 years. The authors inferred that this correlation value varies prominently with age for both sexes, which needs to be investigated further. CONCLUSIONS: The authors suggest that CCT is a noteworthy source of variation in IOP measurements for males as well as females belonging to different age groups, when assessing IOP as a risk for glaucoma in the Punjabi population.

A community-based bacteriological study of quality of drinking-water and its feedback to a rural community in Western Maharashtra, India.

A longitudinal study of the bacteriological quality of rural water supplies was undertaken for a movement towards self-help against diseases, such as diarrhoea, and improved water management through increased community participation. Three hundred and thirteen water samples from different sources, such as well, tank, community standpost, handpumps, percolation lakes, and streams, and from households were collected from six villages in Maharashtra, India, over a one-year period. Overall, 49.8% of the 313 samples were polluted, whereas 45.9% of the samples from piped water supply were polluted. The quality of groundwater was generally good compared to open wells. Irregular and/or inadequate treatment of water, lack of drainage systems, and domestic washing near the wells led to deterioration in the quality of water. No major diarrhoeal epidemics were recorded during the study, although a few sporadic cases were noted during the rainy season. As a result of a continuous feedback of bacteriological findings to the community, perceptions of the people changed with time. An increased awareness was observed through active participation of the people cutting across age-groups and different socioeconomic strata of the society in village activities.

Reno-colo-cutaneous fistula. A case report.

Reno-colo-cutaneous fistula due to genito-urinary tuberculosis is extremely rare. We describe one such case which was successfully managed by single stage surgery (nephroureterectomy, fistulectomy and primary repair of colon) and anti-tubercular treatment.