Development of novel strategies for higher fermentative biohydrogen recovery along with novel metabolites from organic wastes: The present state of the art.

Depletion of fossil fuels and environmental concern has compelled us to search for alternative fuel. Hydrogen is considered as a dream fuel as it has high energy content (142 kJ g-1 ) and is not chemically bound to carbon. At present, fossil fuel-based methods for producing hydrogen require high-energy input, which makes the processes expensive. The major processes for biohydrogen production are biophotolysis, microbial electrolysis, dark fermentation, and photofermentation. Fermentative hydrogen production has the additional advantages of potentially using various waste streams from different industries as feedstock. Novel strategies to enhance the productivity of fermentative hydrogen production include optimization in pretreatment methods, integrated fermentation systems (sequential and combined fermentation), use of nanoparticles as additives, metabolic engineering of microorganisms, improving the light utilization efficiency, developing more efficient photobioreactors, etc. More focus has been given to produce biohydrogen in a biorefinery approach in which, along with hydrogen gas, other metabolites (ethanol, butyric acid, 1,3-propanediol, etc.) are also produced, which have direct/indirect industrial applications. In present review, various emerging technologies that highlight biohydrogen production methods as effective and sustainable methods on a large scale have been critically reviewed. The possible future developments are also outlined.

Sequential Dark-Photo Batch Fermentation and Kinetic Modelling for Biohydrogen Production Using Cheese Whey as a Feedstock.

The present work describes the utilisation of cheese whey to produce biohydrogen by sequential dark-photo fermentation. In first stage, cheese whey was fermented by Enterobacter aerogenes 2822 cells in a 2 L double-walled cylindrical bioreactor to produce hydrogen/organic acids giving maximum biohydrogen yield and cumulative hydrogen of 2.43 ± 0.12 mol mol-1 lactose and 3270 ± 143.5 mL at cheese whey concentration of 105 mM lactose L-1. The soluble metabolites of dark fermentation when utilised as carbon source for photo fermentation by Rhodobacter sphaeroides O.U.001, the yield, and cumulative hydrogen was increased to 4.22 ± 0.20 mol mol-1 VFA and 3800 ± 170 mL, respectively. Meanwhile, an overall COD removal of about 38.08% was also achieved. The overall biohydrogen yield was increased from 2.43 (dark fermentation) to 6.65 ± 0.25 mol mol-1 lactose. Similarly, the modelling for biohydrogen production in bioreactor was done using modified Gompertz equation and Leudeking-Piret model, which gave adequate simulated fitting with the experimental values. The carbon material balance showed that acetic acid, lactic acid, and CO2 along with microbial biomass were the main by-products of dark fermentation and comprised more than 75% of carbon consumed.

Fermentative molecular biohydrogen production from cheese whey: present prospects and future strategy.

Waste-dependent fermentative routes for biohydrogen production present a possible scenario to produce hydrogen gas on a large scale in a sustainable way. Cheese whey contains a high portion of organic carbohydrate and other organic acids, which makes it a feasible substrate for biohydrogen production. In the present review, recent research progress related to fermentative technologies, which explore the potentiality of cheese whey for biohydrogen production as an effective tool on a large scale, has been analyzed systematically. In addition, application of multiple response surface methodology tools such as full factorial design, Box-Behnken model, and central composite design during fermentative biohydrogen production to study the interactive effects of different bioprocess variables for higher biohydrogen yield in batch, fed-batch, and continuous mode is also discussed. The current paper also emphasizes computational fluid dynamics-based simulation designs, by which the substrate conversion efficiency of the cheese whey-based bioprocess and temperature distribution toward the turbulent flow of reaction liquid can be enhanced. The possible future developments toward higher process efficiency are outlined.

Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial.

BACKGROUND: Oral cholera vaccines consisting of killed whole cells have been available for many years, but they have not been used extensively in populations with endemic disease. An inexpensive, locally produced oral killed-whole-cell vaccine has been used in high-risk areas in Vietnam. To expand the use of this vaccine, it was modified to comply with WHO standards. We assessed the efficacy and safety of this modified vaccine in a population with endemic cholera. METHODS: In this double-blind trial, 107 774 non-pregnant residents of Kolkata, India, aged 1 year or older, were cluster-randomised by dwelling to receive two doses of either modified killed-whole-cell cholera vaccine (n=52 212; 1966 clusters) or heat-killed Escherichia coli K12 placebo (n=55 562; 1967 clusters), both delivered orally. Randomisation was done by computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for the patient to seek treatment in a health-care facility. We undertook an interim, per-protocol analysis at 2 years of follow-up that included individuals who received two completely ingested doses of vaccine or placebo. We assessed first episodes of cholera that occurred between 14 days and 730 days after receipt of the second dose. This study is registered with ClinicalTrials.gov, number NCT00289224. FINDINGS: 31 932 participants assigned to vaccine (1721 clusters) and 34 968 assigned to placebo (1757 clusters) received two doses of study treatment. There were 20 episodes of cholera in the vaccine group and 68 episodes in the placebo group (protective efficacy 67%; one-tailed 99% CI, lower bound 35%, p<0.0001). The vaccine protected individuals in age-groups 1.0-4.9 years, 5.0-14.9 years, and 15 years and older, and protective efficacy did not differ significantly between age-groups (p=0.28). We recorded no vaccine-related serious adverse events. INTERPRETATION: This modified killed-whole-cell oral vaccine, compliant with WHO standards, is safe, provides protection against clinically significant cholera in an endemic setting, and can be used in children aged 1.0-4.9 years, who are at highest risk of developing cholera in endemic settings. FUNDING: Bill & Melinda Gates Foundation, Swedish International Development Cooperation Agency, Governments of South Korea, Sweden, and Kuwait.

Evaluation of the immunogenicity and safety of an indigenously developed DTwP-Hib tetravalent combination vaccine (Shan 4) with EasyFourTM in Indian infants administered per EPI schedule: a phase III trial.

The study was planned to assess and compare immunogenicity and safety of an indigenous DTPw-Hib combination vaccine (Shan 4) with EasyFour, the available DTwP-Hib vaccine in India. Overall 210 healthy infants, six to eight weeks of age, were randomized to receive three doses of either Shan 4 or EasyFour at 6, 10 and 14 weeks of age. Antibodies were analyzed prior to and four to six weeks post third vaccine dose. Solicited and unsolicited local and systemic events in the follow up period after each dose were recorded. Post vaccination 100% of the infants in Shan 4 and EasyFour groups had seroprotective concentrations of Anti PRP-T IgG antibodies, IgG anti-diphtheria toxoid antibodies and IgG anti-tetanus toxoid antibodies. Following third dose of vaccination 86.99% subjects in the Shan 4 group and 73.85% subjects in the EasyFour group seroconverted for anti-pertussis antibody titres. Two Serious Adverse Events (SAE s) were reported during the course of the study, all unrelated to the respective vaccine administered. Most commonly reported adverse events in both the groups were pain at injection site, mild fever (<103°F) and minor swelling at injection site. The study proved that Shan 4 was safe and immunogenic compared to the available licensed vaccine.

Effect of change in renal replacement therapy modality on laboratory variables: a cohort study from the UK Renal Registry.

BACKGROUND: Although previous comparisons have shown differences in biochemical and haematological variables between patients on haemodialysis and peritoneal dialysis and those with functioning transplants, these could be due to case mix rather than being due to differences in the types of renal replacement therapy (RRT). The longitudinal follow-up of individual patients after the change in modality has not hitherto been described. METHODS: From the UK Renal Registry (UKRR) database of patients receiving RRT between 1 January 1997 and 31 December 2004, we identified two cohorts: 2033 patients who had been on either haemodialysis (HD) or peritoneal dialysis (PD) for at least a year and who subsequently underwent transplantation and then survived at least a year (PD + HD to Tp); and 892 patients who had been on PD for at least a year who changed to HD and then survived at least a year (PD to HD). In both cohorts, the following variables were studied for the four quarters before and after the change of modality: blood haemoglobin and serum, ferritin, albumin, bicarbonate, cholesterol, calcium, phosphate and parathyroid hormone (PTH) concentrations. No information on drug treatment was available. RESULTS: In the PD + HD to Tp cohort, transplantation was associated with a rise in haemoglobin, albumin and bicarbonate, a fall in ferritin and phosphate, no change in calcium, a fall (but not to normal) in PTH and a transient rise in cholesterol concentrations. In the PD to HD group, the change in modality was associated with a significant temporary fall in haemoglobin, a progressive rise in ferritin, albumin, phosphate and PTH, no change in calcium and fall in bicarbonate and cholesterol concentrations. CONCLUSION: The change from HD to PD is associated with a significant fall in the haemoglobin concentration; anticipation of this change might enable clinicians to ameliorate it. Persistent hyperparathyroidism is common after kidney transplantation.

A comparison of immunogenicity and safety of indigenously developed liquid (DTwPHB-Hib) pentavalent combination vaccine (Shan 5) with Easyfive (liq) and TritanrixHB + Hiberix (lyo) in Indian infants administered according to the EPI schedule.

The study was planned to assess and compare the immune response and safety of an indigenous DTPwHB-Hib pentavalent liquid combination vaccine (Shan 5) with Easyfive and TritanrixHB+ Hiberix, the two available pentavalent combination vaccines. Four hundred infants were randomized to receive three doses of either Shan 5 or one of the two comparators. Antibody analysis was performed prior to and four to six weeks post third vaccine dose. Solicited local and systemic events upto three days and unsolicited adverse events in the 30 days follow up period after each dose were recorded. A total of 365 subjects completed the study. Four to six weeks after third dose, 98.32% of the subjects in Shan 5 group had seroprotective Anti PRP-T IgG antibody concentrations (> or =0.15 microg/mL) as compared to 100% and 98.94% subjects in TritanrixHB + Hiberix and Easyfive groups respectively. Seroprotective levels for Anti-HBs (> or =10 mIU/mL) were observed in 97.77%, 97.83% and 98.94% subjects in Shan 5, TritanrixHB + Hiberix and Easyfive groups respectively. Comparable immune responses were observed for the three other components (D, T and P) in all the groups. Four Serious Adverse Events (SAEs) were reported (three with Shan 5 and one with Easyfive), all unrelated to the respective vaccines. Most commonly reported adverse events in all the groups were pain at injection site, mild fever (<103 degrees F) and minor swelling at injection site. The study proved that Shan 5 was safe and immunogenic compared to the two other licensed vaccines.

An inactivated enterovirus 71 vaccine is safe and immunogenic in healthy adults: A phase I, double blind, randomized, placebo-controlled, study of two dosages.

BACKGROUND: Hand, foot and mouth disease (HFMD), especially that caused by enterovirus 71 (EV71) infection, is a public health concern in the Asia-Pacific region. We report a phase I clinical trial of an EV71 candidate vaccine (INV21) based on a binary ethylenimine inactivated B2 sub-genotype formulated with aluminum hydroxide. METHODS: In this double-blind, placebo-controlled, randomized, dose escalation study adult volunteers received two vaccinations 28 days apart of low or high dose formulations of the candidate vaccine and were then monitored for safety and reactogenicity for four weeks after each dose, and for their immune responses up to 28 weeks. RESULTS: Of 36 adults enrolled, 35 completed the study as planned. Either no or mild adverse events were observed, mainly injection site pain and tiredness. Seroconversion was 100% after two vaccinations. High geometric mean neutralizing antibody titers (GMT) were observed 14 days post first dose, peaking 14 days post second dose (at Day 42) in both high and low dose groups; GMTs on days 14, 28, 42, and 56 were 128, 81, 323, 203 and 144, 100, 451, 351 in low- and high-dose groups, respectively. Titers for both doses declined gradually to Day 196 but remained higher than baseline and the placebo groups, which had low GMTs throughout the duration of the study. Cross-neutralizing antibody activity against heterologous sub-genotypes was demonstrated. CONCLUSION: These data show that the EV71 candidate vaccine is safe and immunogenic in adults and supports further clinical development as a potential pediatric vaccine by initiating a dose-escalation study for determining the dose-dependent safety and immunogenicity of the vaccine in young naïve children.

New adult patients starting renal replacement therapy in the UK in 2005 (chapter 3).

In 2005, the acceptance rate for renal replacement therapy (RRT) in adults in the UK was 108 per million population (pmp). This was derived from complete data for adults in the UK, as data were obtained separately from the five English renal units not currently returning to the Registry. In addition, 87 children started RRT (see Chapter 13) giving a total incidence of 110 pmp. From 2001 to 2005 there has been an 7.3% rise in the acceptance numbers in those 42 renal units with full reporting throughout that period. In the UK, for adults in 2005, the crude acceptance rates in Local Authorities (LA) varied from 0 (in two very small LA areas in Scotland and Northern Ireland) to 271 pmp; the standardized rate ratios for acceptance varied from 0 to 2.76. Excluding the two areas with null returns, 20 areas had significantly low ratios, all of them in England. Thirty had significantly high ratios, seven in Northern Ireland, four in Scotland, three in Wales and seven in London. Over the period 2001-2005, 25 areas had a significantly low standardized acceptance rate; 24 in England and one in Scotland. All except one of these had ethnic minority populations of <10%. Thirty-seven had high standardized acceptance rates, seven in Scotland where ethnicity data were not available, 14 from areas with ethnic minority populations in excess of 10%, and 12 were in Wales or the Southwest of England. The median age of patients starting RRT in England has increased from 63.8 years in 1998 to 65.2 years in 2005. The median age of incident non-White patients is significantly lower at 56.8 years. In England, the acceptance rate is highest in the 75-79 age band at 408 pmp, as in Scotland at 580 pmp; in Wales the peak is in the 80-84 age band at 525 pmp, as in Northern Ireland with a rate of 825 pmp. Diabetic renal disease (20%) remains the most common specific primary renal disease. There was a significant positive correlation between the percentage of incident RRT patients with diabetic renal disease and the percentage of non-Whites in the incident cohort. Haemodialysis (HD) was the first modality of RRT in 76% of patients, peritoneal dialysis (PD) in 21% and pre-emptive transplant in 3%. In 1998, the proportion whose first modality was HD was 58% and this continues to increase. By day 90, 8% had died, a further 1% had stopped treatment or been transferred out leaving 91% of the original cohort on RRT. Of these, 71% were on HD, 26% on PD and 3% had received a transplant. Data on first referral to a nephrologist were available from 22 centres for the period 2000-2005 (for a total of 5611 patients and 59 centre-years). In 2005, the mean percentage of patients referred late (<90 days before dialysis initiation) was 30% (centre range 13-48%). This was similar to the value in 2000. Patients referred late were older, a higher proportion of them were male, a lower proportion non-White, and a lower proportion with no recorded comorbidity. Patients with polycystic kidney disease and diabetic nephropathy tended to be referred early compared with the whole incident cohort and those with uncertain aetiology and no recorded diagnosis referred late. Estimated GFR (eGFR) at the start of RRT appears to be higher in older than younger patients. eGFR is significantly lower in those referred late compared with those referred earlier and this is especially marked in the older patients. The geometric mean eGFR of all patients starting RRT rose from 6 in 1997 to above 7.5 in 2003, since when it has remained stable.

All patients receiving renal replacement therapy in the United Kingdom in 2005 (chapter 4).

Summary data are provided for the whole United Kingdom. There were 41,776 adult patients alive on renal replacement therapy (RRT) in the UK at the end of 2005, a prevalence for adults of 694 pmp. Addition of 748 children under the age of 18 on RRT gives a total prevalence of 706 pmp. The more detailed analysis includes data on 37,534 patients from 65 of the 70 units which returned detailed data to the Registry: all in Northern Ireland, Scotland and Wales, and 45 of the 50 units in England. The annual increase in prevalence in the 38 renal units participating in the Registry since 2000 was 5.0%. There is substantial variation in the crude Local Authority area prevalence from 299 pmp to 1275 pmp. In general, areas with large ethnic minority populations had high standardized prevalence ratios (SPR). Nevertheless several Local Authority areas in South Wales (Methyr Tydfil, Swansea and Rhondda/Cynon/Taff) had a higher SPR than would be predicted from the local ethnic mix. Another group in North West England (Bury, Rochdale, Oldham and Salford), had a lower SPR than expected from the local ethnic mix. The median age of prevalent patients on RRT was 56.6 years, that of patients on HD 64.5 years, PD 59.2 years and transplanted patients 49.7 years. The median vintage of the whole RRT population was 5.1 years: that of transplanted patients was 9.8 years, HD patients 2.8 years and PD patients 2.1 years. The maximal prevalence rate (SPR) occurred in men (2270 pmp) in the 75-79-year age band and women (1144 pmp) in the 65-74-year age band. Of RRT patients in the UK, 45% had a transplant, 41.7% were on centre-based haemodialysis and 12% on peritoneal dialysis. The proportion of patients on home haemodialysis remained very small (1.2%) in spite of the recent NICE guidelines. The haemodialysis population is continuing to expand, mainly through growth in the proportion of patients undergoing dialysis in satellite units. The peritoneal dialysis population is continuing to contract in spite of the small but progressive rise in automated PD. The most common identifiable diagnosis in those under 65 was glomerulonephritis (18.0%) and in those over 65 it was diabetes (13.4%). One-year survival rates of prevalent patients in the different centres contributing to the UK Renal Registry are presented. The centres agreed to remove anonymity. There is no evidence of any significant differences in survival of prevalent patients between UK centres. The one-year survival of prevalent dialysis patients increased significantly from 1998 to 2004 in England (83.3% to 87.1% P = 0.0001 for linear trend), Scotland (84.0% to 87.0% P = 0.023 for linear trend) and Wales (83.4% to 86.1% P = 0.027 for linear trend). The test for non-linearity in this trend (indicating that there has been a large increase which is now tailing off) was significant for England and Wales.

Haemodialysis dose and serum bicarbonate (chapter 7).

Data from 21 renal units was insufficient to allow analyses of the dose of dialysis in those units. Amongst the remainder, there is evidence of a progressive increase in the proportion of patients meeting the Renal Association audit standard for urea reduction ratio (URR). In the UK as a whole, 81% of prevalent haemodialysis patients met the standard for URR in 2005. Greater achievement of the standard in a given unit is associated with a higher median URR in that unit, although there is some evidence that some units have been able to narrow the distribution of achieved URR values. Achievement of the standard remains, as in previous years' Reports, less common amongst patients recently established on haemodialysis compared with those established on haemodialysis for longer. Correction of acidosis, as measured by serum bicarbonate concentration remains highly variable, although there is continued uncertainty about the interpretation of routine measurements of venous serum bicarbonate concentration in haemodialysis patients. Overall, approximately 64% of UK haemodialysis patients, and 50% of peritoneal dialysis patients met the Renal Association standard for serum bicarbonate in 2005.

The UK Vascular Access Survey--follow-up data and repeat survey (chapter 5).

In the 2006 Vascular Access Survey, 51% of all patients commenced renal replacement therapy (RRT) using definitive access. Of patients commencing on haemodialysis HD, 37% commenced with definitive access (31% in the 2005 survey). Of those known to the renal units for a year or more, only half started HD with definitive access. Around 4% of patients currently receiving HD were in-patients. Around 30% of staphylococcal line infections were methicillin resistant Staphylococcus aureus (MRSA), which was similar to the 2005 survey. At 6 months after starting RRT, 76% of live patients were using definitive access [defined as the use of peritoneal dialysis (PD), transplant, arteriovenous fistula (AVF) or arteriovenous graft (AVG)] and at 12 months it was 80%. Of the HD patients starting RRT in April 2005, 65% started using venous catheters, at 6 months this had fallen to 35% and at 12 months to 30%. The use of non-tunnelled lines was <1% by 6 months. The proportion on PD had fallen slightly at 12 months (from 20% to 16%) by which time 11% had received a transplant, 1% had recovered and 18% had died. Data returns for the 2006 survey were returned from 37/74 renal units compared with returns from 62 units in the 2005 survey.

Incidentally detected clear cell renal cell carcinoma with rhabdoid differentiation.

Renal cell carcinoma with rhabdoid differentiation (RCC-R) has an aggressive biologic behavior and poor prognosis. A recent consensus statement of the International Society of Urological Pathology (ISUP) proposed a nucleolar grading system (ISUP grade) for RCC to replace Fuhrman system and recommended reporting the presence of rhabdoid differentiation and considering tumors with rhabdoid differentiation to be ISUP Grade 4. We report a case of incidentally detected clear cell RCC-R in a 52-year-old man. This is one of the earliest cases of RCC-R (pT1b) detected and first such case from Indian subcontinent.

High expression of integrin ß6 in association with the Rho-Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers.

Integrin αvß6 is involved in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast. In addition, integrin ß6 (ITGB6) is of prognostic value in invasive breast cancers, particularly in HER2+ subtype. However, pathways mediating the activity of integrin αvß6 in clinical progression of invasive breast cancers need further elucidation. We have examined human breast cancer specimens (N = 460) for the expression of integrin ß6 (ITGB6) mRNA by qPCR. In addition, we have examined a subset (N = 147) for the expression of αvß6 integrin by immunohistochemistry (IHC). The expression levels of members of Rho-Rac pathway including downstream genes (ACTR2, ACTR3) and effector proteinases (MMP9, MMP15) were estimated by qPCR in the HER2+ subset (N = 59). There is a significant increase in the mean expression of ITGB6 in HER2+ tumors compared to HR+HER2- and triple negative (TNBC) subtypes (P = 0.00). HER2+ tumors with the highest levels (top quartile) of ITGB6 have significantly elevated levels of all the genes of the Rho-Rac pathway (P-values from 0.01 to 0.0001). Patients in this group have a significantly shorter disease-free survival compared to the group with lower ITGB6 levels (HR = 2.9 (0.9-8.9), P = 0.05). The mean level of ITGB6 expression is increased further in lymph node-positive tumors. The increased regional and distant metastasis observed in HER2+ tumors with high levels of ITGB6 might be mediated by the canonical Rho-Rac pathway through increased expression of MMP9 and MMP15.

Safety and efficacy of an indigenous recombinant interferon-alpha-2b in patients with chronic myelogenous leukaemia: results of a multicentre trial from India.

BACKGROUND: Compared to hydroxyurea, treatment with interferon-alpha (IFN-alpha) is known to prolong survival in patients with chronic phase of chronic myelogenous leukaemia (CML) and was considered as first-line therapy till recently. We conducted a multicentre trial using an indigenous recombinant IFN-alpha-2b to evaluate its efficacy and toxicity in chronic phase CML. METHODS: Between September 2000 and August 2001, patients with chronic phase CML were recruited within 8 weeks of diagnosis at 7 centres in India. The study was approved by the Ethics Committee of each participating Institute and Informed, written consent was obtained from all patients. All patients were given the study drug in a dose of 5 million units daily subcutaneously. Response and survival analyses were done with intent-to-treat analysis. RESULTS: One hundred and fourteen patients (75 men and 39 women) were included in the study. Their ages ranged from 18 to 62 years (median 37 years). Fifty-seven per cent of patients had a haematological response; complete response in 31.6% and partial response in 25.4%. The median time to achieve complete haematological response was 6 months (range 3-12 months). Cytogenetic response was seen in 39.4% of patients; complete in 1.8%, partial in 28% and minimal in 9.6%. The median time to achieve partial and complete cytogenetic response was 6 and 12 months, respectively. Nineteen patients had progression (blast crisis n=15, accelerated phase n=4) while on treatment. Two patients refused further treatment after the initial 4 weeks due to IFN-a toxicity, mainly bone pains and fever. The major toxic effects of treatment were fever (78%), fatigue (25.4%) and myalgia (52%). No patient died of toxicity. Currently, 95 patients are alive, 91 in the chronic phase and 4 in the accelerated phase. Four patients were lost to follow up and all 15 patients with blast crisis died of progressive disease at a median Interval of 6.5 months (range 1-15 months). The Kaplan-Meier probability of survival at 36 months was 76%. CONCLUSION: This study confirms the efficacy of the indigenous recombinant IFN-alpha-2b in chronic phase CML. The drug has a toxicity profile similar to that of other preparations.

Safety and efficacy of an indigenous human recombinant interferon alpha 2b (Shanferon) in patients with chronic hepatitis B.

Interferon treatment is the established option for the treatment of patients with chronic hepatitis B without decompensated liver disease. However, such treatment is expensive. We report here our data of a multi-center, open-label trial of the use of an indigenously produced interferon in the treatment of chronic HBeAg-positive chronic hepatitis B. Adult patients with chronic HBeAg-positive hepatitis B with elevated serum transaminase activity and positive serum HBV DNA test were treated with 5 MU/day of an indigenously produced interferon (Shanferon; Shantha Biotechnics, Hyderabad, India) for 4 months, and were then followed up for 6 months. Of the 39 patients enrolled, 36 completed the treatment and 33 completed the post-treatment follow-up. Of the 33 patients who completed the study, end-of-treatment biochemical and virological responses were observed in 10 (30%) and 5 (15%) respectively. Sustained biochemical and virological responses were observed in 15 (45%) and 7 (21%), patients respectively. Adverse effects led to the discontinuation of treatment in only one patient. Our data suggest that safety and efficacy of the indigenously produced interferon were similar to those previously reported results with interferon from other sources.

Indigenous recombinant streptokinase vs natural streptokinase in acute myocardial infarction patients: Phase III multicentric randomized double blind trial.

BACKGROUND: Streptokinase is the most widely used thrombolytic agent and can now be made using recombinant DNA technology. The present trial was initiated to assess an indigenous recombinant streptokinase (Shankinase, r-SK). AIM: To compare the efficacy and safety of indigenous recombinant streptokinase (Shankinase, r-SK) and natural streptokinase (Streptase, n-SK). SETTINGS AND DESIGN: Double blind, randomized, non-inferiority, multicentric, parallel study. MATERIALS AND METHODS: Patients of AMI < 6 hours of chest pain and 2 mm ST elevation in 2 contiguous chest leads V(1)-V(6) or 1 mm in limb leads were randomized to receive 1.5 miu of either r-SK or n-SK. CK Peaking and decrease of > or = 50% ST segment were used to assess reperfusion. STATISTICAL ANALYSIS: Difference in the groups was assessed by chi-square or paired t test as required. Probability value < 0.05 was considered significant with 95% confidence interval. RESULTS: Overall 150 patients were recruited (96 r-SK group and 54 in n-SK group) and demographic and clinical profile of the groups was comparable. Reperfusion was seen in 68.2% (58) and 69.4% (34) patients in r-SK and n-SK groups respectively. Commonly seen adverse events were fever in 7 (8.5%), hypotension in 3 (3.6%), nausea in 2 (2.4%) patients. Minor bleeding were seen in 4 (4.8%) of patients. CONCLUSION: Indigenous recombinant Streptokinase (r-SK) is as efficacious as natural streptokinase (n-SK) in establishing reperfusion as assessed by non-invasive parameters with comparable side effect profile.

Immunogenicity and safety of hepatitis B vaccine (Shanvac-B) using a novel pre-filled single use injection device Uniject in Indian subjects.

BACKGROUND: Hepatitis B is a major public health problem, which has now been controlled to some extent by vaccination especially with the recombinant hepatitis B vaccine, which has been proven to be safe and efficacious since its introduction in the 1990s. But problems of unsafe injection practices still persist. Now newer delivery devices like uniject are available for making vaccination very safe. OBJECTIVE: To evaluate the immunogenicity and safety of the Hepatitis-B (Shanvac-B) vaccine in Uniject pre-filled device administered to healthy adults and infants at 0, 1, 2 months schedule. METHODS: A total of 122 healthy subjects (62 adults and 60 infants) were administered three doses of the recombinant Hepatitis-B vaccine using Uniject pre-filled device. Blood samples for antibody titer estimation were taken before vaccination and 4-6 weeks after third dose. Subjects, parents or guardians were given diary cards to record any adverse reactions. RESULTS: Protective immune responses to the vaccine were seen in 96.4% of adults and 100% of infants who completed the study. The Geometric Mean Titers (GMT) in adults and infants were 518.5 and 385.41 mIU/ml respectively. Mild fever, itching, and swelling at injection site were the most common side effects observed. CONCLUSION: The safety and immunogenicity of the Hepatitis B Vaccine in the novel pre-filled device Uniject was effectively demonstrated in the present study.

Efficacy of a low-cost, inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a randomized, controlled trial.

BACKGROUND: Killed oral cholera vaccines (OCVs) have been licensed for use in developing countries, but protection conferred by licensed OCVs beyond two years of follow-up has not been demonstrated in randomized, clinical trials. METHODS/PRINCIPAL FINDINGS: We conducted a cluster-randomized, placebo-controlled trial of a two-dose regimen of a low-cost killed whole cell OCV in residents 1 year of age and older living in 3,933 clusters in Kolkata, India. The primary endpoint was culture-proven Vibrio cholerae O1 diarrhea episodes severe enough to require treatment in a health care facility. Of the 66,900 fully dosed individuals (31,932 vaccinees and 34,968 placebo recipients), 38 vaccinees and 128 placebo-recipients developed cholera during three years of follow-up (protective efficacy 66%; one-sided 95%CI lower bound = 53%, p<0.001). Vaccine protection during the third year of follow-up was 65% (one-sided 95%CI lower bound = 44%, p<0.001). Significant protection was evident in the second year of follow-up in children vaccinated at ages 1-4 years and in the third year in older age groups. CONCLUSIONS/SIGNIFICANCE: The killed whole-cell OCV conferred significant protection that was evident in the second year of follow-up in young children and was sustained for at least three years in older age groups. Continued follow-up will be important to establish the vaccine's duration of protection. TRIAL REGISTRATION: ClinicalTrials.gov NCT00289224.

Immune responses following one and two doses of the reformulated, bivalent, killed, whole-cell, oral cholera vaccine among adults and children in Kolkata, India: a randomized, placebo-controlled trial.

Immune responses after one and two doses of the reformulated killed oral cholera vaccine were measured in a double-blind, randomized, placebo-controlled trial of 77 adults aged 18-40 years and 77 children aged 1-17 years residing in Kolkata, India. 65% of adults and 87% of children and 46% of adults and 82% of children exhibited a > or =4-fold rise in serum Vibrio cholerae O1 vibriocidal antibody titers from baseline following dose 1 and 2, respectively. Responses to V. cholerae O139 were less pronounced but followed a similar pattern. We demonstrate that in a cholera-endemic area, the vaccine elicited vibriocidal responses after a single-dose of the vaccine.