PubMed Health⌕ Search

Biomedical subjects

Pankaj Jay Pasricha

Publications and source records attributed to Pankaj Jay Pasricha.

14 recordsLinked to original sources
PubMed2007

Neural stem cells for the treatment of disorders of the enteric nervous system: strategies and challenges.

The main goal of this review is to summarize the status of the research in the field of stem cells transplantation, as it is applicable to the treatment of gastrointestinal motility. This field of research has advanced tremendously in the past 10 years, and recent data produced in our laboratories as well as others is contributing to the excitement on the use of neural stem cells (NSC) as a valuable therapeutic approach for disorders of the enteric nervous system characterized by a loss of critical neuronal subpopulations. There are several sources of NSC, and here we describe therapeutic strategies for NSC transplantation in the gut. These include using NSC as a relatively nonspecific cellular replacement strategy in conditions where large populations of neurons or their subsets are missing or destroyed. As with many other recent "breakthroughs" stem cell therapy may eventually prove to be overrated. However, at the present time, it does appear to provide the hope for a true cure for many currently intractable diseases of both the central and the peripheral nervous system. Certainly more extensive research is needed in this field. We hope that our review will encourage new investigators in entering this field of research ad contribute to our knowledge of the potentials of NSC and other cells for the treatment of gastrointestinal dysmotility.

Animals↗
PubMed2006

Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder.

1. The effectiveness of antimuscarinic agents in the treatment of the overactive bladder (OAB) syndrome is thought to arise through blockade of bladder muscarinic receptors located on detrusor smooth muscle cells, as well as on nondetrusor structures. 2. Muscarinic M3 receptors are primarily responsible for detrusor contraction. Limited evidence exists to suggest that M2 receptors may have a role in mediating indirect contractions and/or inhibition of detrusor relaxation. In addition, there is evidence that muscarinic receptors located in the urothelium/suburothelium and on afferent nerves may contribute to the pathophysiology of OAB. Blockade of these receptors may also contribute to the clinical efficacy of antimuscarinic agents. 3. Although the role of muscarinic receptors in the bladder, other than M3 receptors, remains unclear, their role in other body systems is becoming increasingly well established, with emerging evidence supporting a wide range of diverse functions. Blockade of these functions by muscarinic receptor antagonists can lead to similarly diverse adverse effects associated with antimuscarinic treatment, with the range of effects observed varying according to the different receptor subtypes affected. 4. This review explores the evolving understanding of muscarinic receptor functions throughout the body, with particular focus on the bladder, gastrointestinal tract, eye, heart, brain and salivary glands, and the implications for drugs used to treat OAB. The key factors that might determine the ideal antimuscarinic drug for treatment of OAB are also discussed. Further research is needed to show whether the M3 selective receptor antagonists have any advantage over less selective drugs, in leading to fewer adverse events.

Animals↗
PubMed2006

Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis.

Chronic pancreatitis (CP) is a relatively common disorder, characterized by glandular insufficiency and chronic, often intractable, pain. The mechanism of pain in CP is poorly understood. We have previously developed a model of trinitrobenzene sulphonic acid (TNBS)-induced CP that results in nociceptive sensitization in rats. This study was designed to examine changes in the excitability and alteration of voltage-gated K(+) currents of dorsal root ganglia (DRG) neurons innervating the pancreas. CP was induced in adult rats by an intraductal injection of TNBS. DRG neurons innervating the pancreas were identified by 1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate fluorescence labeling. Perforated patch-clamp recordings were made from acutely dissociated DRG neurons from control and TNBS-treated rats. Pancreas-specific DRG neurons displayed more depolarized resting potentials in TNBS-treated rats than those in controls (P < 0.02). Some neurons from the TNBS-treated group exhibited spontaneous firings. TNBS-induced CP also resulted in a dramatic reduction in rheobase (P < 0.05) and a significant increase in the number of action potentials evoked at twice rheobase (P < 0.05). Under voltage-clamp conditions, neurons from both groups exhibited transient A-type (I(A)) and sustained outward rectifier K(+) currents (I(K)). Compared with controls, the average I(A) but not the average I(K) density was significantly reduced in the TNBS-treated group (P < 0.05). The steady-state inactivation curve for I(A) was displaced by approximately 20 mV to more hyperpolarized levels after the TNBS treatment. These data suggest that TNBS treatment increases the excitability of pancreas-specific DRG neurons by suppressing I(A) density, thus identifying for the first time a specific molecular mechanism underlying chronic visceral pain and sensitization in CP.

Action Potentials↗
PubMed2006

Biliary drainage by using stents without a central lumen: a pilot study.

BACKGROUND: Despite several attempts to make the conventional tubular stents with a central lumen for flow less susceptible to a biofilm buildup and thereby prevent clogging, this goal has remained elusive. We hypothesized that the creation of pathways for fluid flow around the stent instead of through it would avoid this problem. The aim of our study was to report the development and the evaluation of a novel lumen-less stent. METHODS: By using a software computer modeling, a 10F "winged" stent was designed. A pilot feasibility study was performed by using a prototype of this stent for endoscopic biliary drainage in 5 patients with malignant biliary obstruction. OBSERVATIONS: Modeling data revealed that the winged stent offers a larger surface area for flow, higher velocity of flow, and increased flow rates compared with the conventional tubular stent. In the clinical trial, there was a significant decrease of serum bilirubin after the placement of this stent (serum bilirubin before and 2 weeks after stent placement, 14.94 +/- 5.7 mg/dL vs. 2.86 +/- 1.4 [p < 0.004]), accompanied by radiologic evidence of decompression of the biliary system. CONCLUSIONS: We have shown that it is possible to provide adequate biliary drainage by using a stent without a lumen. Such a design may have potential clinical advantages over existing designs.

Aged↗
PubMed2006

Immediate endoscopic closure of colon perforation by using a prototype endoscopic suturing device: feasibility and outcome in a porcine model (with video).

BACKGROUND: Perforation is an uncommon but potentially devastating complication of colonoscopy. Surgical closure is the standard of care. Immediate endoluminal closure of a perforation would avoid the morbidity and mortality associated with general anesthesia, laparotomy, and surgical repair. OBJECTIVES: To evaluate the feasibility and safety of full-thickness endoscopic closure of colonic perforations with a prototype endoscopic suturing device, the Eagle Claw, in a porcine model. DESIGN: Endoscopic animal experimental study of closure of colon perforation by using a porcine model. SUBJECTS: Ten pigs were included in the study. INTERVENTIONS: The Eagle Claw was used to close small perforations (1.5 to 2 cm) of the colon created by needle-knife with the animal under general anesthesia by using the endoluminal route. All animals received intravenous antibiotics and were allowed to eat after 24 hours. MAIN OUTCOME MEASUREMENTS: The animals were monitored daily for signs of sepsis and peritonitis. On day 7, they were euthanized. The peritoneal cavity was examined for fecal peritonitis, and the colon perforation site was checked for wound dehiscence and pericolic abscess formation. RESULTS: Endoscopic closure of the colon perforation was successful in 7 animals, and they recovered well without any sepsis or peritonitis. Necropsy did not reveal fecal peritonitis or pericolonic abscess formation at the site of perforation, and the perforation healed well. Closure was successful in 1 animal, but necropsy revealed dehiscence of the colon perforation site. Endoscopic closure was unsuccessful in 2 animals, and these were euthanized immediately. CONCLUSIONS: Closure of acute perforation of the colon is feasible with the Eagle Claw endoscopic suturing device in a porcine model.

Animals↗
PubMed2005

Molecular and behavioral changes in nociception in a novel rat model of chronic pancreatitis for the study of pain.

The approach to the management of painful chronic pancreatitis has been empirical, primarily due to the lack of information about biological mechanisms producing pain. To facilitate research into pain mechanisms, our aim was to assess a rat model of chronic pancreatitis induced by pancreatic infusion of trinitrobenzene sulfonic acid as a model of painful pancreatitis. Nociception was assessed by measuring mechanical sensitivity of the abdomen and by recording the number of nocifensive behaviors in response to electrical stimulation of the pancreas. Expression of neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) in the thoracic dorsal root ganglia receiving input from the pancreas and nerve growth factor (NGF) in the pancreas were measured. Rats with pancreatitis exhibited marked increase in sensitivity to mechanical probing of the abdomen and increased sensitivity to noxious electrical stimulation of the pancreas. There were significant increases in NGF protein in the pancreas and in expression of neuropeptides CGRP and SP in the sensory neurons from dorsal root ganglia receiving input from the pancreas. We have established quantitative measures of referred nociception and pancreatic hyperalgesia in a rat model of chronic pancreatitis that bears histological similarities to the human disease. This model has considerable construct, face and predictive validity for the human condition. It is of importance for the study of the pathogenesis of pain in this condition and can facilitate the development of new therapeutic options.

Amylases↗
PubMed2005

Neural stem cell transplantation in the stomach rescues gastric function in neuronal nitric oxide synthase-deficient mice.

BACKGROUND & AIMS: Nitric oxide is a major inhibitory neurotransmitter in the enteric nervous system. Loss or dysfunction of nitrinergic neurons is associated with serious disruptions of motility, intractable symptoms, and long-term suffering. The aim of this study was to evaluate the effect of intrapyloric transplantation of neural stem cells (NSCs) on gastric emptying and pyloric function in nNOS-/- mice, a well-established genetic model of gastroparesis. METHODS: NSCs were isolated from embryonic mice transgenically engineered to express green fluorescent protein and transplanted into the pylorus of nNOS-/- mice. Grafted cells were visualized in pyloric sections and further characterized by immunofluorescence staining. One week posttransplantation, gastric emptying to a non-nutrient meal was measured using the phenol red method and pyloric function was assessed by measuring the relaxation of pyloric strips in an organ bath in response to electrical field stimulation (EFS) under nonadrenergic, noncholinergic conditions. RESULTS: One week following implantation, grafted NSCs differentiated into neurons and expressed neuronal nitric oxide synthase. Gastric emptying was significantly increased in mice that received NSCs as compared with vehicle-injected controls (49.67% vs 35.09%; P < .01 by Student t test). EFS-induced relaxation of pyloric strips was also significantly increased (P < .01 by 2-way analysis of variance). The nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester and the neuronal blocker tetrodotoxin blocked the EFS-induced relaxation, indicating that the observed effect is NO mediated and neuronally derived. CONCLUSIONS: Our results support the potential of NSC transplantation as a viable therapeutic option for neuroenteric disorders.

Animals↗
PubMed2004

A novel shape-locking guide for prevention of sigmoid looping during colonoscopy.

BACKGROUND: Looping of the endoscope in the sigmoid colon and other colonic segments often represents a significant challenge to the performance of comfortable, complete, and swift colonoscopy. This report describes the design and operation of a new device that addresses this problem, together with preliminary preclinical experience with this use of this shape-locking guide (SG-1). METHODS: The shape-locking guide is an overtube that can be converted from a flexible to a rigid configuration on demand. When in the rigid configuration, the shape-locking guide is designed to protect the colon wall from lateral forces exerted by the colonoscope. The shape-locking guide was evaluated in vitro by using an artificial colon model to learn how to operate it, and to assess feasibility for prevention of colon looping. In addition, safety was assessed in vivo in a pig model. RESULTS: In vitro, the shape-locking guide prevented colonic looping and, thereby, aided completion of "colonoscopy" in the artificial colon model. Subsequent in vivo studies demonstrated that use of the shape-locking guide is safe and feasible; it performed well with respect to ease of insertion and avoidance of sigmoid looping. There was no evidence of significant injury to the colon or adjacent abdominal viscera. CONCLUSIONS: This preliminary study shows that use of the shape-locking guide is safe and that it has performance characteristics that may assist the performance of colonoscopy. Human trials are being undertaken.

Animals↗
PubMed2003

Origins and patterns of spontaneous and drug-induced canine gastric myoelectrical dysrhythmia.

The aim of this study was to investigate the characteristics and orientation of gastric dysrhythmia using multichannel serosal recordings in dogs. Ten dogs chronically implanted with four to eight pairs of electrodes were studied. Gastric slow waves were recorded in four sessions: postsurgical and after atropine, vasopressin, and glucagon. A total of 554.7 min of bradygastria, 201 min of tachygastria and 22.3 min of arrhythmia were observed in the recordings. The majority of bradygastria (80.5 +/- 9.4%) originated in the proximal stomach (P < 0.04, vs other locations) and propagated all the way to the distal antrum. In contrast, tachygastria mainly originated in the distal antrum (80.6 +/- 8.8%) (P < 0.04, vs other locations) and propagated partially or all the way to the proximal stomach. Dysrhythmia appeared intermittently with normal gastric slow waves. In all recordings, normal slow waves were present 38.0 +/- 5.3% of the time, while bradygastria, tachygastria, and arrhythmia were present 35.9 +/- 5.3%, 23.0 +/- 1.6%, and 2.4 +/- 0.5% of the time, respectively. The prevalence of dysrhythmia was highest in the distal antrum (80.4%) (P < 0.01) and lowest in the proximal part of the stomach. In conclusion, tachygastria originates from an ectopic pacemaker in the distal antrum. It may completely or partially override the normal slow waves. Bradygastria is attributed to a decrease in the frequency of the normal pacemaker in the corpus. The prevalence of gastric dysrhythmia is different in different locations of the stomach and is highest in the distal antrum.

Analysis of Variance↗