Determining Rates of Molecular Secretion from Supernatant Concentration Measurements in a 3D-Bioprinted Human Liver Tissue Model.

The secretion rate of albumin is a key indicator of function in liver tissue models used for hepatotoxicity and pharmacokinetic testing. However, it is not generally clear how to determine molecular secretion rates from measurements of the molecular concentration in supernatant media. Here, we develop computational and analytical models of molecular transport in an experimental system that enable determination of albumin secretion rates based on measurements of albumin concentration in supernatant media. The experimental system is a 3D-bioprinted human liver tissue construct embedded in a 3D culture environment made from packed microgel particles swollen in liquid growth media. The mathematical models reveal that the range of albumin synthesis rates necessary to match experimentally measured albumin concentrations corresponds to reaction-limited conditions, where a steady state of albumin spatial distribution is rapidly reached between media exchanges. Our results show that temporally resolved synthesis rates can be inferred from serial concentration measurements of collected supernatant media. This link is critical to confidently assessing in vitro tissue performance in applications where critical quality attributes must be quantified, like in drug development and screening.

Changes in salivary output after induction at high-altitude areas and its effects on dental caries among Indian Army troops.

BACKGROUND: This study was aimed to evaluate the changes in salivary output and its effect on dental caries among Indian troops after 6 months of stay at high-altitude area (HAA). METHODS: All troops undergo mandatory dental checkup during acclimatization phase before deployment at HAA. Two thousand troops who fulfilled inclusion and exclusion criteria were selected, and consent for the study was obtained. Stimulated and unstimulated salivary samples were collected, the decayed, missing, and filled teeth (DMFT) index was evaluated, and required dental treatment was completed. The same salivary samples were collected after 6 months (on deinduction) to evaluate the salivary output. The DMFT index was re-evaluated to check the initiation of caries. RESULTS: The mean values of unstimulated and stimulated saliva at the initial visit were 4.105 and 17.03 gm, respectively, whereas the mean values of unstimulated and stimulated saliva after 180 days were 3.034 and 15.831 gm, respectively. Salivary flow was found to be significantly decreased after 6 months both in unstimulated and stimulated saliva. The mean DMFT at the time of induction of the study was 6.18 ± 3.03, and on deinduction, it was 7.22 ± 3.45 with p < 0.001, which was highly statistically significant. CONCLUSION: A decrease in body fluids and changed sympathetic and parasympathetic at HAA lead to decreased salivary secretions. Low water intake, high carbohydrate solid diet, negligible supply of fresh food, difficulty in maintenance of oral hygiene, and overall stress due to loneliness are all contributory factors for an increase in dental caries. It clearly demonstrates that prolonged stay at HAA affects salivary volume outflow, both stimulated and unstimulated, which has a corresponding effect on new caries.

Powering Precision' in OAD Management....from Diagnosis to Delivery.

Achieving asthma control remains an elusive goal for the majority of patients worldwide. Pressurized metered-dose inhalers (pMDIs) are the cornerstone of asthma treatment. Despite a better understanding of the pathophysiology of asthma, presence of reliable diagnostic tools, availability of a wide array of effective and affordable inhaled drugs and simplified national and international asthma management guidelines, asthma remains poorly managed in India. However, nonadherence rates for long-term inhaler therapy among adults are estimated to exceed 50%. Nonadherence is associated with unfavorable clinical outcomes and diminished quality of life. The pMDI is an economic and portable medication delivery system, but the device does not indicate how much medicine remains in the canister once a patient starts using it. Lack of a dose counter makes determining the number of remaining doses in an MDI problematic. The addition of an SIMPLE, ACCURATE and RELIABLE digital dose counter to an inhaler can improve patient satisfaction. More trials are needed to determine the merits of different treatments and strategies for patients with inadequately controlled severe persistent asthma and to identify patients likely to benefit from new treatment options.

Guiding Principles for the use of Fluroquinolones in Out-patient Community Settings of India: Panel Consensus.

INTRODUCTION: Respiratory tract infections have been an important cause of morbidity and mortality worldwide that is looming large especially in context of antibiotic resistance that is confronted both by a pulmonologist as well as a general practitioner. A reflection to this trend has been the rising phenomenon of MICs as shown the respiratory pathogens towards conventional antibiotics including macrolides or ß lactam/ß lactamase inhibitor combinations. Respiratory fluoroquinolones offer broad yet potent cover of respiratory pathogens leading to their obvious choice for empirical therapy for clinical persisters or high risk cases with prior history of antibiotics not-withstanding the clinical concerns in tropical countries. AIM: To further assess the clinical role of respiratory quinolones in outpatient settings of India especially in line with the known endemicity of chronic infections or tuberculosis. METHODS: Cross-sectional, national survey questionnaire survey to explore the clinical perceptions, attitude and insights on the clinical use of respiratory fluoroquinolones was rolled out amongst pulmonologists and consultant physicians practicing respiratory medicine in India. Descriptive statistics was utilized to describe the numerical and categorical data. RESULTS: Nationwide representative sample of fourteen pulmonologists provided response and clinical insight on the current management strategies for community acquired pneumonia (CAP) with 'respiratory' fluoroquinolones. Each of the doctor in the panel agreed that the ideal antibiotic for the treatment in CAP or lower respiratory tract infection (LRTI) should be highly effective with lesser side effects and broader spectrum covering atypical bacteria. Doctors agreed that most the fixed dose combination (FDC) has gone into disrepute probably because of pharmacokinetic incompatibility that could have further fuelled the epidemic of antibiotic resistance. 9 (64%) doctors suggested that there is omnipresence if not overwhelming presence of patient poor response to beta-lactam or fluoroquinolones in clinical practice. It was agreed that fluoroquinolones would be the rightful choice for patients with prior history of antibiotic use with or without comorbidities. Amongst the newer fluoroquinolones available, Garenoxacin offers broad and potent action against resistant strains for CAP. Despite the overwhelming concern of tropical infection in Indian context, Garenoxacin could be considered for mono- or add-on therapy in moderate to severe yet stable cases of CAP. Short course therapy of 5 to 10 days should offer no complimentary masking of anti-mycobacterial activity since the relevant minimum inhibitory concentration (MIC90) are high that are beyond the comprehension of suggested therapeutic dose of 400 mg tablets. CONCLUSIONS: The growing incidence of Macrolide resistance suggests the clinical role of new generation fluoroquinolones including Garenoxacin as a clinically useful therapeutic strategy for moderate to severe CAP as monotherapy or in combination.

Infliximab vs. adalimumab in Crohn's disease: results from 327 patients in an Australian and New Zealand observational cohort study.

BACKGROUND: Maintenance anti-tumour necrosis factor-α (anti-TNFα) treatment for Crohn's disease is the standard of care for patients with an inadequate response to corticosteroids and immunomodulators. AIM: To compare the efficacy and safety of infliximab and adalimumab in clinical practice and assess the value of concomitant immunomodulator therapy. METHODS: We performed an observational cohort study in consecutive patients with Crohn's disease qualifying for anti-TNFα treatment in Australia and New Zealand between 2007 and 2011. Demographic and clinical data were prospectively recorded to identify independent factors associated with induction and maintenance of response to infliximab or adalimumab, or to either anti-TNFα therapy. RESULTS: Three hundred and twenty-seven patients (183 infliximab, 144 adalimumab) successfully applied for treatment. Eighty-nine percent responded in all groups and median maintenance of response was similar for the two agents. Concomitant immunomodulator with infliximab, but not adalimumab, demonstrated a significantly longer response overall (P = 0.002), and significantly fewer disease and treatment-related complications (P = 0.017). Corticosteroids at baseline, and/or in the preceding 12 months, were associated with a 9-13 times greater risk of disease flare during maintenance treatment as compared to no corticosteroids (P < 0.0001). Maintenance of response was similar in the anti-TNF naïve and anti-TNF experienced subgroups. CONCLUSIONS: In this large, real-life study, we demonstrate infliximab and adalimumab to have similar response characteristics. However, infliximab requires concomitant immunomodulator to achieve optimal maintenance of response comparable to adalimumab monotherapy. The results of this study will assist clinicians in further optimising patient care in their day-to-day clinical practice.

Exploring the hidden potential of fosfomycin for the fight against severe Gram-negative infections.

Gram-negative resistance is a serious global crisis putting the world on the cusp of 'pre-antibiotic era'. This serious crisis has been catalysed by the rapid increase in carbapenem-resistant Enterobacteriaceae (CRE). Spurge in colistin usage to combat CRE infections leads to the reports of (colistin and carbapenem resistant enterobacteriaceae) CCRE (resistance to colistin in isolates of CRE) infections further jeopardising our last defence. The antibacterial apocalypse imposed by global resistance crisis requires urgent alternative therapeutic options. Interest in the use of fosfomycin renewed recently for serious systemic infections caused by multidrug-resistant Enterobacteriaceae. This review aimed at analysing the recent evidence on intravenous fosfomycin to explore its hidden potential, especially when fosfomycin disodium is going to be available in India. Although a number of promising evidence are coming up for fosfomycin, there are still areas where more work is required to establish intravenous fosfomycin as the last resort antibacterial for severe Gram-negative infections.

Necrotizing Fasciitis of Hand By Methicillin Resistant Staphylococcus aureus (MRSA) - A Sinister.

Necrotizing fasciitis (NF) is an aggressive and life-threatening infection of skin and soft tissue characterized by widespread fascial necrosis, leads to gross morbidity and mortality if left untreated. Although MRSA has become a common isolate associated with skin and soft tissue infections globally over the past few years, monomicrobial MRSA NF has been reported only in a few studies. Our case represents the development of NF followed by trivial trauma salvaged with daptomycin and amputation of the affected limb. Prompt diagnosis and surgical management with empiric MRSA cover in areas where community acquired MRSA (CA-MRSA) is endemic for suspected cases of necrotizing fasciitis can prevent the dreaded consequences.

A prescription event monitoring study on the utility of garenoxacin, a newer fluoroquinolone in India.

BACKGROUND: Prescription event monitoring (PEM) study is conducted worldwide. The main objective of such study is to monitor the adverse events when a drug is being prescribed in "real life clinical" settings. PEM studies are being looked upon as an essential observational tool of postmarketing surveillance. Garenoxacin, a newer fluoroquinolone offers an excellent spectrum of antimicrobial coverage, which includes Gram-positive, Gram-negative, anaerobes and atypical microorganism. This broad spectrum of activity is attributed to its unique structure. AIM: The aim was to assess the safety profile of garenoxacin in Indian settings. MATERIALS AND METHODS: A total of 400 doctors across the country participated in the study. Data from 12,498 patients was obtained. Monitoring of each patient was done for any adverse events. RESULTS: As an initial line of therapy garenoxacin was preferred in majority of cases of community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis. Adverse events were reported in 159 patients which included 0.5% cases with nausea/vomiting, 0.1% cases with diarrhea. Central nervous system side-effects like drowsiness or dizziness was reported in 0.02% of the cases. All the adverse events were of mild to moderate severity and did not require hospitalization. CONCLUSION: Garenoxacin a novel desfluoroquinolone appears to be an ideal antimicrobial agent for the treatment of various respiratory tract infections including CAP. With superior safety profile, excellent antimicrobial coverage and a convenient once a day dosing garenoxacin appears to improve the patient compliance.

In Vitro Fractional Inhibitory Concentration (FIC) Study of Cefixime and Azithromycin Fixed Dose Combination (FDC) Against Respiratory Clinical Isolates.

INTRODUCTION: Acute respiratory infections (ARI) contribute to more than 75% of health care seeking in primary health care facilities in India. Respiratory tract infections (RTIs) are managed frequently by ß-lactam, macrolide and fluroquinolone class of antibiotics. However, these recommended classes of antibiotic have shown resistance in community settings. Antibiotic combinations may provide broader spectrum not only in terms of coverage but also to overcome multiple resistance mechanisms overcoming individual class limitations. AIM: The study aimed to determine In vitro interactions interpreted according to calculated fractional inhibitory concentration (FIC) index between cefixime and azithromycin against common respiratory clinical isolates. MATERIALS AND METHODS: Forty four bacterial respiratory clinical isolates from microbiology department of tertiary care hospital from Mumbai were used to determine the minimum inhibitory concentration (MIC) values of cefixime and azithromycin. Synergy testing of cefixime combination with azithromycin was performed by checkerboard method. Interaction was determined according to calculated FIC index. RESULTS: MIC values were ranging from 2-128 µg/ml and 0.24-128 µg/ml for cefixime and azithromycin respectively against K.pneumoniae, M.catarrhalis, S.pneumoniae and H.influenzae isolates. All the tested isolates were resistant to cefixime. Azithromycin resistance was noted in all the isolates except six M. catarrhalis isolates. FIC index showed synergy and additive effect in 66% (29/44) and 34% (15/44) all bacterial clinical isolates. Maximum synergy between cefixime and azithromycin was observed against K. pneumoniae in 91% isolates. CONCLUSION: This is one of the first attempts to check the rationality of fixed dose antibiotic combination of cefixime and azithromycin in India market. Though results of this study cannot be generalized considering the limitations of low sample size and in vitro model, our data provides stepping stone for further validation of cefixime and azithromycin fixed dose combinations (FDCs) in clinical setting by conducting randomized controlled trials. We think that judicious and rational use of FDCs may help to reduce the risk of selection of further drug resistance along with better clinical outcome.

Garenoxacin in Skin and Skin Structure Infections Sustained due to Road Traffic Accident.

Skin and soft tissue infections represent a continuum of symptoms that range from uncomplicated cellulitis to the potentially lethal entity necrotizing fasciitis that is often considered to be microbial invasions of the epidermis, dermis and subcutaneous tissues. Garenoxacin, a newer oral des-fluoroquinolone having potent antimicrobial activity against wide variety of common pathogens involved in skin and skin structure infections (SSTIs), including the resistant strains offer the advantage of broad spectrum of coverage including gram positive, gram negative and anaerobic organisms. This case study indicates the utility of garenoxacin in treating skin and soft tissue infections caused by road traffic accidents.

Health outcome and safety assessment of a fixed dose combination of Amantadine, Paracetamol, Chlorpheniramine maleate, and Phenylephrine introduction in India: A prescription event monitoring study.

To assess the likely impact of a fixed dose combination (FDC) of Amantadine, Paracetamol, Chlorpheniramine maleate, and Phenylephrine on the health outcome and safety profile arising from the complementary action of amantadine and other ingredients, we conducted a Prescription Event Monitoring study for patients with suspected Influenza symptoms who were prescribed this FDC in 'real life clinical settings' or clinical practice. Between August 2010 and March 2011, Questionnaires were sent to doctors who provided data on the health outcome or safety profile. Sedation and allergy, including rash, were noted in few of the patients. None of the patients reported any major events. Most of the patients (60%) were initiated on FDC therapy within the first 24 hours of symptom onset. Even as a significant proportion of the patients (24.9%) had a concurrent history of allergy / rhinitis including asthma, few of them (4.1%) reported lack of improvement and had to be complemented with antibiotics. The FDC of Amantadine, Chlorpheniramine, Paracetamol, and Phenylephrine was found to be safe and well-tolerated when administered to patients within the first 24 to 48 hours of symptom onset.

Effect of carbonated drink on excisional palatal wound healing: a study on Wistar rats.

BACKGROUND: Millions of people worldwide consume carbonated drinks every day. The effects of these drinks on hard tissues in the mouth have been proved beyond doubt. Only a little has been done so far to assess the effects of carbonated drinks on oral soft tissues. This study was an attempt to assess the effect of carbonated drinks on oral wound healing. MATERIALS AND METHODS: Twenty female Wistar rats were considered for the study. A circular wound was created on the palate and the animals were divided into two groups (experimental and control group). The experimental group animals were fed with a commercially available carbonated drink instead of water, and two animals from each group were euthanized at 3, 7, 14 and 21 days. Wound site was assessed morphometrically and histologically. RESULTS: There was a marked difference in the healing pattern between the experimental group and control group animals. Control group animals showed a normal healing pattern with formation of a fibrous connective tissue at the end of 21 days. In the experimental group, healing was delayed and disrupted. The wound site showed a definite palatal perforation in experimental group animals after 14 days, but osteoclasts were not noticed in the histological sections. CONCLUSION: Consumption of carbonated drinks can disrupt oral wound healing. Results suggest that the bone changes seen in experimental group samples are not mediated by osteoclasts, and acidity of the carbonated drinks could be one of the reasons for these changes.

Spigelion hernia: fascia lata repair is an alternative option in absence of prolene mesh.

Spigelian hernia is rare. Seven cases of Spigelian hernia are presented. These include two recurrent Spigelian hernias. Incisional hernias through Spigelian aponeurosis after Pfannensteil incision are not included. Clinical examination is the mainstay of diagnosis. The true incidence is possibly higher, as a low Spigelian hernia is not recognised and often diagnosed as a direct inguinal hernia. Ultrasound scanning is recommended, as it is non-invasive and easily available and can detect the hernial orifice in the Spigelian fascia at an early stage. Recurrence of Spigelian hernia took place in two cases through the site of prolene stitch of a previous repair. Hernioplasty with tension free fascia lata graft/prolene mesh was carried out in all cases. The cost of fascia lata graft is only a scar in the thigh. In a mean follow-up of 3.1 -year no patient has reported back with recurrence This is the ideal substitute for the patients in developing countries where synthetic meshes are still not freely available.

Comparison and classification of dental arch forms of Indian and Chinese subjects with normal occlusions.

To compare the dental arch forms of Indian and Chinese subjects, 30 untreated Indian and 30 untreated Chinese adults with normal occlusion and symmetrical arches were examined. The arches were classified as narrow, wide, mid, pointed and flat, according to the method developed by Monique Raberin etal., from Lyon, France. For the sample examined the Chinese population was found to have significantly wider arches compared to the Indian population.