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Biomedical subjects

P Vohra

Publications and source records attributed to P Vohra.

At least 19 recordsLinked to original sources

Inflammatory bowel disease.

Till about 3 decades ago, inflammatory bowel disease (IBD) was considered as non-existent in our country. However, since that time several reports of IBD, mainly ulcerative colitis have been published. More recently, Crohn's disease is also being reported from the country. This trend of UC appearing first in a population followed by CD also appears to be true in other developing nations. A substantial increase in the rates of CD over UC in the last few decades is reported from developed nations as well. Of the other epidemiological factors, an increased risk of CD and lower risk of UC in smokers is established in adults. However, it appears that smoking increases the risk of IBD in children. The etiology of IBD remains elusive. Within the triad of genetics, immunity and antigen responsible for the development of IBD, maximum advances have been made in the field of immune aberrations and this is being exploited to treat the disease. It is well established that IBD results from a disordered immune system in the gut, in response to an unidentified antigen in a predisposed individual. The immune response is enhanced and revolves around antigen-presenting cells, CD 4 T-lymphocytes and tumor necrosis factor alpha. CD results from an enhanced Th1 activity. The pathogenesis of UC is less clear but appears to be humoral. Advances in diagnostics include the availability of serology, ultrasound and nuclear scans, none of which have been tried in our setting where infectious diseases and tuberculosis is rampant. Growth failure and the importance of nutrition in IBD, especially CD, cannot be underemphasized. In many situations nutritional interventions have been used solely as a form of therapy for CD. Newer steroid molecules with minimal systemic effects are also being considered. Other treatment options highlighted are the use of immunosuppressive agents, biologic agents and role of surgery.

Adult↗

A pilot study of posttraumatic stress and nonadherence in pediatric liver transplant recipients.

BACKGROUND: Symptoms of posttraumatic stress disorder (PTSD) were described in survivors of life-threatening diseases, the trauma being the experiences associated with the disease or its treatment. Their prevalence in liver transplant recipients is unknown. Based on clinical observations, we hypothesize that a significant proportion of pediatric liver transplant recipients suffers from PTSD symptoms. We further hypothesize that nonadherence (noncompliance) to medical management may, in some cases, be associated with these symptoms. Traumatized patients, according to this hypothesis, will avoid taking their medications, because these serve as painful reminders of the disease. OBJECTIVES: To determine the prevalence of PTSD symptoms in a sample of pediatric liver transplant recipients. To determine whether symptoms of PTSD are associated with nonadherence in these patients. To describe the clinical presentation of PTSD and the management of severe nonadherence in patients who suffer from this disorder. METHODS: Nineteen pediatric liver transplant recipients and their caretakers were interviewed, using the UCLA Post Traumatic Stress Disorder Reaction Index (PTSRI). Data were obtained on a few demographic parameters and perception of disease threat. Adherence was evaluated by 2 methods: 1) a clinician panel (taking into account the clinical sequelae of severe nonadherence); and 2) computation of the standard deviations (SDs) of consecutive determinations of blood levels of Tacrolimus (a higher SD means higher variability between individual measures and is therefore an indicator of nonadherence). As an illustration of the general phenomenon, we describe 3 cases of liver transplant recipients who were nonadherent and who suffered from PTSD. RESULTS: Six of 19 patients had positive scores on all 3 components of the PTSRI (PTSD patients). Three of these, and none of the others, were considered significantly nonadherent by the panel. Therefore, nonadherence was significantly associated with the existence of symptoms from all 3 domains of PTSD (Fisher's exact test) in our sample. In particular, a high avoidance score on the PTSRI was highly correlated with panel-determined nonadherence. Further, SD of medication levels were significantly higher in PTSD patients, compared with the rest of our sample. No significant differences were found in perception of disease threat or demographic variables between PTSD patients and the rest of our sample. The 3 cases that we describe became adherent to their medications when symptoms of PTSD subsided during the course of therapy. CONCLUSIONS: Clinically significant nonadherence, determined by 2 different methods, was associated with the full spectrum of PTSD symptoms in this sample. It was especially associated with a high avoidance score, which suggests that avoidance of reminders of the disease (eg, medications) may be a mechanism of nonadherence. Screening for and management of these symptoms, therefore, may improve adherence. This novel concept may be applicable to other patient populations. However, more data are needed before any definite conclusions can be drawn.

Adolescent↗

Induction of cytotoxic T-cell responses following oral immunization with synthetic peptides encapsulated in PLG microparticles.

CTL responses play a critical role in clearing viral infections. We have investigated the potential of poly(lactide-co-glycolide) (PLG) microparticles as an oral delivery system for peptides representing CTL epitopes from measles virus nucleoprotein. Oral administration of CTL epitopes encapsulated in 50:50 PLG microparticles, resulted in vivo priming of splenic peptide-specific CTL responses. However, the observed CTL lysis was low and cofeeding of encapsulated peptide with cholera toxin as a mucosal adjuvant did not result in any significant enhancement of the observed CTL responses. The pronounced immunostimulatory effect of microparticles, combined with their excellent tissue compatibility and biodegradability makes them a valuable delivery system for synthetic peptide immunogens. However, further work is needed to improve their efficiency via the oral route.

Administration, Oral↗

CTL responses induced by a single immunization with peptide encapsulated in biodegradable microparticles.

A synthetic peptide representing a measles virus (MV) cytotoxic T cell epitope (CTL) when encapsulated in poly (D,L-lactide co-glycolide) (PLG) 50:50 microparticles induced a strong CTL response after a single intraperitoneal immunization of mice which was greater than that following administration of the peptide in Freund's complete adjuvant. A 100 micrograms dose of encapsulated peptide was shown to be more effective for CTL priming than 50 and 25 micrograms doses. A vaccine formulation prepared by simply mixing empty 50:50 PLG microparticles with the peptide resulted in the induction of CTL responses comparable to those induced by the encapsulated peptide. Moreover, a CTL response against MV-infected target cells was observed. These findings highlight the potential immunostimulatory effect of PLG microparticles for the induction of MV and peptide-specific CTL responses.

Amino Acid Sequence↗

Mucosal immunization with a measles virus CTL epitope encapsulated in biodegradable PLG microparticles.

The immunogenicity of a cytotoxic T cell epitope (CTL) representing residues 52-60 from measles virus (MV) nucleoprotein, encapsulated in poly(lactide-co-glycolide) (PLG) microparticles was evaluated after mucosal immunization. After intranasal administration of the encapsulated CTL epitope linked at the carboxyl terminus of two copies of a T-helper epitope (TT-NP6), peptide-specific and MV-specific CTL responses were detected in splenocytes. However, these responses were lower than the responses observed when the TT-NP6 peptide was administered intranasally in saline or using CTB as an adjuvant. Intranasal coadministration of the encapsulated TT-NP6 peptide with CTB did not result in any significant potentiation of the CTL responses. The effectiveness of biodegradable PLG microparticles for mucosal delivery of CTL epitopes, combined with their excellent tissue compatibility and biodegradability suggests that they represent a valuable delivery system for synthetic immunogens. However, further work is needed to define the requirements for effective absorption by the nasal epithelium.

Animals↗

Priming of measles virus-specific CTL responses after immunization with a CTL epitope linked to a fusogenic peptide.

In this study, the potential of the amino-terminal sequence from the F1 polypeptide responsible for the fusion of measles virus (MV) with cell membranes as a carrier system for a CTL epitope from the MV nucleoprotein was examined. The addition of the fusion sequence (FP) at either the amino or the carboxyl terminus of the CTL epitope peptide rendered it immunogenic after intraperitoneal immunization in mice. The CTLs induced were able to lyse target cells pulsed with the peptide or persistently infected with MV. After intranasal administration of a FP-CTL chimera with or without cholera toxin B subunit (CTB) as an adjuvant, CTL responses to the peptide pulsed and to MV-infected target cells were detected. Responses in groups of mice where CTB was used as an adjuvant were stronger. However, intranasal administration of the CTL epitope did not induce a protective response against intracranial challenge with a neuroadapted strain of MV. These findings highlight the potential of fusion sequences as a carrier system for CTL epitopes and the potential of the intranasal route for administration of synthetic peptides representing MV sequences.

Amino Acid Sequence↗

Biodegradable microparticles as a delivery system for measles virus cytotoxic T cell epitopes.

Cytotoxic T-cell (CTL) responses are likely to be important for the clearance of a measles virus (MV) infection. To induce CTL responses. replicating vectors have generally been used but the use of such vectors in humans mav be problematic, and immunization with synthetic peptides may be more appropriate. We have investigated the potential of poly(lactide-co-glycolide)(PLG) microparticles as a delivery system for a CTL epitope representing residues 51-59 from MV nucleoprotein. After a single intraperitoneal injection in saline of the encapsulated epitope, CTL responses to the homologous peptide and MV were detected over a period of 4 months. Responses reached a maximum 30 days after priming and were maintained at high levels for 120 days. These responses were higher than those observed when the CTL epitope was administered in saline or as an emulsion in Incomplete Freund's Adjuvant. The pronounced immunostimulatory effect of microparticles, combined with their excellent tissue compatibility and biodegradability suggests that they represent a valuable delivery system for synthetic peptide immunogens.

Animals↗

Induction of measles virus-specific cytotoxic T-cell responses after intranasal immunization with synthetic peptides.

We have investigated the structural requirements for the induction of cytotoxic T-cell responses (CTL) in vivo after intranasal immunization with an immunodominant CTL epitope from the nucleoprotein of measles virus (MV). For the induction of CTL responses, covalent linkage of the CTL epitope to a helper T-cell epitope was required and the orientation of the epitopes influenced the immunogenicity of the CTL epitope. The presence of two copies as compared with one copy of a T-helper epitope, rendered the CTL epitope more immunogenic and resulted in the in vivo induction of MV-specific CTLs without the need for an adjuvant. The role of CTL responses to this epitope in protection after intranasal administration was evaluated in a mouse model against challenge with a neuroadapted strain of MV. Although a decreased mortality in the peptide immunized compared with that in unimmunized mice was observed, the protection achieved was not significant. These findings highlight the importance of the rational design of synthetic immunogens for the induction of CTL responses and the potential of the intranasal route for immunization.

Adjuvants, Immunologic↗

Effect of diet on growth and plasma ascorbic acid in chicks.

Six experiments were conducted to study the effect of diet on growth and plasma ascorbic acid in chickens. D-Glucuronolactone failed to improve growth with either a crude yeast-fish meal diet or a purified diet based on casein and gelatin. With the purified diet, D-glucuronic acid and L-gulonolactone also failed to improve growth and did not influence plasma ascorbic acid levels. Dietary ascorbic acid improved growth of chicks with a purified diet in most cases, but not with a corn-soybean diet. Meat meal and fish meal caused slight increases in plasma ascorbic acid, whereas soybean meal, safflower meal, and cottonseed meal caused greater increases when used in a purified diet. Gulonolactone oxidase activity in the kidney was not different between chicks fed the purified or the corn-soybean diets, but was reduced by 0.1% dietary ascorbic acid. The mechanism for the increase in plasma ascorbic acid with the addition of soybean meal and other plant protein sources to the diet is not known.

Animals↗

Effect of halofuginone (Stenorol) on Chukar partridge (Alectoris chukar).

This study was conducted to assess the effect of the coccidiostat halofuginone (Stenorol) on growth, feed consumption, and survival of Chukar partridge. Halofuginone was fed to three replicates (14 chicks per replicate) of chukar chicks from 2 to 7 d of age at levels of 0, 1.5, 3.0, 6.0 and 12 ppm. Mortality from 2 to 7 d was 0, 0, 0, 11, and 21 birds, respectively, by treatment. Seven-day body weight showed a significant linear decrease with increasing halofuginone level (P < 0.01). On the 7th d, replicates receiving 6.0 and 12.0 ppm halofuginone were transferred to unmedicated feed for the remainder of the test due to excessive mortality. The other groups were continued until 6 wk of age. At 6 wk, chicks fed 6 or 12 ppm halofuginone from 2 to 7 d and then unmedicated feed did not differ in body weight from those fed the unmedicated control diet. A significant difference in mortality was not observed among the other three treatment groups to 6 wk of age. A linear depression in 3-, 4-, 5-, and 6-wk body weight with increasing halofuginone level was observed within the first three treatment levels (P < 0.05). It was concluded that 1.5 ppm halofuginone depressed growth of young chukars and that 6 ppm resulted in increased mortality.

Animals↗

Induction of systemic immune responses to measles virus synthetic peptides administered intranasally.

A systemic antibody response was induced when a chimeric peptide containing two copies of a promiscuous T-cell epitope and one copy of a B-cell epitope (TTB) from the fusion protein of measles virus (MV) was administered to mice intranasally without adjuvant. A higher antibody titre was produced when the peptide was administered intranasally with cholera toxin B subunit (CTB) as an adjuvant and these antibodies crossreacted with the MV. Furthermore, splenocytes from intranasally immunized mice proliferated in vitro in the presence of the TTB peptide. The immune response following intranasal immunization with the peptide was influenced by the MHC haplotype of the strain of mice used. Thus CBA and BALB/c mice were high responders whereas C57BL/6 mice were low responders. Although peptide administered intranasally with CTB to CBA mice induced an immune response, no significant protection was observed against intra-cranial challenge with canine distemper virus which is antigenically related to MV.

Administration, Intranasal↗

Nutritional evaluation of grain amaranth for growing chickens.

The nutritional value of raw and autoclaved grain amaranth, its milling fractions (perisperm and bran), fat-free flour, and of popped amaranth was evaluated for growing chickens. The control diet, which was composed primarily of corn and soybean meal, contained 3.06 kcal apparent ME (AME)/g and 23.6% CP. Test diets contained about the same AME and CP levels, and the following levels of the test samples: whole grain amaranth flour, 61.46%; fat-free flour, 62.10%; perisperm, 49.50%; bran, 35.30%; and popped amaranth, 61.10%. Two groups of six unsexed broiler chicks each, 2-day old when received, were used per diet. Chickens fed diets containing autoclaved grain amaranth or its fractions over 17 or 18 days grew as well as those fed the control diet. Feeding of popped amaranth resulted in poorer performance. On a dry matter basis, AME values of raw grain amaranth flour, fat-free flour, perisperm, bran, and popped amaranth were found to be 3.21, 3.09, 3.68, 3.06, and 2.98 kcal/g, respectively. Respective AME values for the first four autoclaved samples were 3.04, 2.94, 3.10, and 3.17 kcal/g. Autoclaved grain amaranth and its perisperm fraction replaced corn in the diets of growing chickens with similar performance results.

Animal Feed↗

Protein and metabolizable energy requirements of hand-fed squabs from hatching to 28 days of age.

Incubator-hatched squabs were hand fed slurries containing 14% diet and 86% water by weight for the 1st 4 days, followed by 20% diet and 80% water for the next 2 to 3 days. From Days 7 to 28, the slurry contained 25% diet and 75% water. A diet containing about 61% isolated soybean protein, 8.9% soybean oil, 21.5% glucose, 4% CaHPO4.2H2O, and 1.3% CaCO3 supplemented with vitamins and trace elements supported the optimum growth of squabs for the first 7 days. It contained 3,675 kcal metabolizable energy (ME)/kg and 53.3% crude protein (CP). The composition of the optimum diet for feeding from Days 7 to 289 was as follows: corn starch, 58.37%; isolated soybean protein, 23.1%; cellulose, 8.0%; soybean oil, 3.0%; CaHPO4.2H2O, 3.0; methionine, .3%; CaCO3, 1.0; plus vitamins and trace minerals. This diet provided 3,200 kcal ME/kg and 20% CP.

Aging↗

Calcium intake in relation to ovulation and oviposition when access to oyster shell is time-restricted or unrestricted.

White Leghorn hens were fed either a conventional diet containing 40 gCa/kg from oyster shell, or one low in Ca (3 g/kg) with oyster shell offered separately. In experiment 1 access to oyster shell was unrestricted; in experiment 2. Access was time-restricted to the first 6 h of the photophase of the 14L:10D photoperiod. Irrespective of time-restriction, hens offered oyster shell laid heavier eggs, but shell thickness was reduced. On days on which only ovulation occurred, time-restricted hens consumed significantly less Ca than unrestricted hens. In contrast, on days on which only oviposition occurred, time-restricted hens consumed significantly more Ca than unrestricted hens. These results suggest that when access to oyster shell is time-restricted to morning hours Ca consumption occurs in response to a Ca deficit persisting from the previous period of shell calcification.

Animals↗