Post-viral Infection Research Articles

Stability of cough reflex sensitivity during viral upper respiratory tract infection (common cold)

Cough is among the symptoms most commonly associated with an acute, viral upper respiratory tract infection (URI), such as the common cold. Two previous studies incorporating capsaicin cough challenge methodology have demonstrated that cough reflex sensitivity is transiently enhanced during URI. These studies used single measurements of cough reflex sensitivity during the URI period. To our knowledge, no previous studies have included multiple measurements of cough reflex sensitivity to capsaicin during a URI to evaluate the stability of this measure during the acute viral illness.In the current methodological investigation, we performed capsaicin cough challenges in 42 subjects with URI who were otherwise healthy, adult, nonsmokers (25 female). Subjects were enrolled within 72 h of onset of illness and randomly assigned to 3 groups (n = 14 each) that underwent cough reflex sensitivity measurement (C2 and C5) at days 0 and 1 for group 1; days 2 and 3 for group 2; or days 4 and 5 for group 3. Each subject returned 4–8 weeks post-viral infection to establish a healthy baseline measurement (recovery).Our results support that cough reflex sensitivity to capsaicin, as measured by C5, is a sensitive measure that remains stable during 6 days of a URI. These results suggest that cough reflex sensitivity measures in the presence of a URI provide a sensitive and reproducible approach that could be used in future investigations seeking to test experimental antitussive therapies.

Screening, isolation and optimization of anti–white spot syndrome virus drug derived from terrestrial plants

To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various terrestrial plants and to evaluate the efficacy of the same in host-pathogen interaction model. Thirty plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti-WSSV property in Litopenaeus vannamei. The best anti-WSSV plant isolate, TP22C was isolated and further analyzed. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug. Seven plant isolates exhibited significant survivability in host. The drug TP22C thus formulated showed 86% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of TP22C required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 750 mg/kg body weight/day survived at the rate of 86%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection. The drug TP22C derived from Momordica charantia is a potent anti-white spot syndrome virus drug.

Screening, isolation and optimization of anti–white spot syndrome virus drug derived from marine plants

To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various marine floral ecosystems and to evaluate the efficacy of the same in host-pathogen interaction model. Thirty species of marine plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti-WSSV property in Litopenaeus vannamei. By means of chemical processes, the purified anti-WSSV plant isolate, MP07X was derived. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug. Nine plant isolates exhibited significant survivability in host. The drug MP07X thus formulated showing 85% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of MP07X required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 1 000 mg/kg body weight/day survived at the rate of 85%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection. The drug MP07X derived from Rhizophora mucronata is a potent anti-WSSV drug.

Prolonged expansion of human nucleus pulposus cells expressing human telomerase reverse transcriptase mediated by lentiviral vector

Human degenerative disc disease (DDD) is characterized by progressive loss of human nucleus pulposus (HNP) cells and extracellular matrix, in which the massive deposition are secreted by HNP cells. Cell therapy to supplement HNP cells to degenerated discs has been thought to be a promising strategy to treat DDD. However, obtaining a large quality of fully functional HNP cells has been severely hampered by limited proliferation capacity of HNP cells in vitro. Previous studies have used lipofectamine or recombinant adeno-associated viral (rAAV) vectors to deliver human telomerase reverse transcriptase (hTERT) into ovine or HNP cells to prolong the activity of nucleus pulposus cells with limited success. Here we developed a lentiviral vector bearing both hTERT and a gene encoding green fluorescence protein (L-hTERT/EGFP). This vector efficiently mediated both hTERT and EGFP into freshly isolated HNP cells. The expressions of both transgenes in L-hTERT/EGFP transduced HNP cells were detected up to day 210 post viral infection, which was twice as long as rAAV vector did. Furthermore, we observed restored telomerase activity, maintained telomere length, delayed cell senescence, and increased cell proliferation rate in those L-hTERT/EGFP transduced HNP cells. Our study suggests that lentiviral vector might be a useful gene delivery vehicle for HNP cell therapy to treat DDD.

Megalocytivirus-induced proteins of turbot (Scophthalmus maximus): Identification and antiviral potential

Megalocytivirus is an important fish pathogen with a broad host range that includes turbot. In this study, proteomic analysis was conducted to examine turbot proteins modulated in expression by megalocytivirus infection. Thirty five proteins from spleen were identified to be differentially expressed at 2days post-viral infection (dpi) and 7dpi. Three upregulated proteins, i.e. heat shock protein 70 (Hsp70), Mx protein, and natural killer enhancing factor (NKEF), were further analyzed for potential antiviral effect. For this purpose, turbot were administered separately with the plasmids pHsp70, pMx, and pNKEF, which express Hsp70, Mx, and NKEF respectively, before megalocytivirus infection. Viral dissemination and propagation in spleen were subsequently determined. The results showed that the viral loads in fish administered with pNKEF were significantly reduced. To examine the potential of Hsp70, Mx, and NKEF as immunological adjuvant, turbot were immunized with a DNA vaccine in the presence of pHsp70, pMx, or pNKEF. Subsequent analysis showed that the presence of pNKEF and pHsp70, but not pMx, significantly reduced viral infection and enhanced fish survival. Taken together, these results indicate that NKEF exhibits antiviral property against megalocytivirus, and that both NKEF and Hsp70 may be used in DNA vaccine-based control of megalocytivirus infection. This study provides the first proteomic picture of turbot in response to megalocytivirus infection. We demonstrated that megalocytivirus infection modulates the expression of turbot proteins associated with various cellular functions, and that one of the upregulated proteins, NKEF, exhibits antiviral effect when overexpressed in vivo, while another upregulated protein, Hsp70, exhibits adjuvant effect when co-immunized with a DNA vaccine. These results add molecular insights into turbot immune response induced by megalocytivirus and provide candidate proteins with application potentials in the control of megalocytivirus-associated disease.

Pharmacokinetics of combined gene therapy expressing constitutive human GM-CSF and hyperthermia-regulated human IL-12

BackgroundAn adenovirus that expresses both interleukin (IL)-12 and granulocyte-macrophage colony-stimulating-factor (GM-CSF) has been proven to be very effective in treating several tumors, but causes serious normal tissue toxicities.MethodsIn this study, a novel adenoviral vector was constructed by placing the human GM-CSF gene under the control of the CMV-IE promoter and human IL-12 gene under the control of heat shock protein 70B gene promoter. Both hGM-CSF and hIL-12 expressions in virus-infected tumor cells were analyzed in vitro and in vivo when underlying single or multiple rounds of hyperthermia.ResultsWe observed constitutive high expression of human GM-CSF and heat-induced expression of human IL-12 after a single round of hyperthermia post viral infection. The heat-induced hIL-12 expression exhibited a pulse-like pattern with a peak at 24 hrs followed by a decline 48 hrs post heat stress. Repeated heat treatment was more effective in inducing hIL-12 expression than a one-time heat treatment. Interestedly, we also observed that constitutive expression of hGM-CSF could be stimulated by heat stress in tested tumor cells.ConclusionOur study provided a novel strategy for combined gene therapy that allows constitutive expression of a non-toxic gene such as GM-CSF and heat-induced expression of a toxic gene such as IL-12. In addition, our study also showed that hyperthermia can be used to trigger gene expression in temporal and special manner.

Selection of normalization factors for quantitative real time RT-PCR studies in Japanese flounder (Paralichthys olivaceus) and turbot (Scophthalmus maximus) under conditions of viral infection

Disease outbreaks caused by iridoviruses are known to affect farmed flounder (Paralichthys olivaceus) and turbot (Scophthalmus maximus). To facilitate quantitative real time RT-PCR (qRT-PCR) analysis of gene expression in flounder and turbot during viral infection, we in this study examined the potentials of 9 housekeeping genes of flounder and turbot as internal references for qRT-PCR under conditions of experimental infection with megalocytivirus, a member of the Iridoviridae family. The mRNA levels of the 9 housekeeping genes in the brain, gill, heart, intestine, kidney, liver, muscle, and spleen of flounder and turbot were determined by qRT-PCR at 24h and 72h post-viral infection, and the expression stabilities of the genes were determined with geNorm and NormFinder algorithms. The results showed that (i) viral infection induced significant changes in the mRNA levels of the all the examined genes in a manner that was dependent on both tissue type and infection stage; (ii) for a given time point of infection, stability predictions made by the two algorisms were highly consistent for most tissues; (iii) the optimum reference genes differed at different infection time points at least in some tissues; (iv) at both examined time points, no common reference genes were identified across all tissue types. These results indicate that when studying gene expression in flounder and turbot in relation to viral infection, different internal references may have to be used not only for different tissues but also for different infection stages.

Lung Cytokine Gene Expression is Correlated with Increased Severity of Disease in a Novel H4N8 Influenza Virus Isolated from Shorebirds

ABSTRACTThe lung cytokine gene expression profiles of mice infected with 2 strains of H4N8 viruses isolated from shorebirds and reference H4 viruses from ducks are compared. Major differences between the two H4N8 strains of shorebirds, one of which causes a severe respiratory disease in mice, are in the PB1 and NS1 genes. In mice with H4N8 virus induced pneumonia, overall expression of TNF-α, IL-6 and IL-12 genes was markedly higher than in mice infected with other H4 viruses tested, although gene expression of type I interferon was not increased until day 4 post viral infection. In contrast, in mice infected with a comparison H4N8 strain, gene expression of type I interferon peaked on day 1 post viral infection. Overall, the cytokine response corresponds with the severity of disease caused by shorebird H4N8 virus. The results obtained in this study provide valuable information to understand the immunopathology induced by a low pathogenic avian influenza virus, which may be useful in preparation for outbreaks of novel influenza A virus.

Parenteral fluids do not affect pulmonary immune responses to influenza or susceptibility to secondary bacterial pneumonia in mice

Animal models of viral respiratory disease often use weight loss as a marker of disease severity; however, this may relate to dehydration and malnutrition that would be corrected clinically. We tested whether parenteral fluid therapy improved weight loss from influenza infection. BALB/c and C57BL/6 mice were infected with A/X31 (H3N2) influenza and randomized to intraperitoneal fluid therapy. Blood glucose was also measured post-viral infection on day 3 and 6 in BALB/c mice and on day 6 in C57BL/6 mice. Parenteral fluids did not alter weight loss or the immunological response to infection, and glucose levels were not abnormal.

DIAGNOSTIC BIOMARKERS OF INFECTIOUS CANINE HEPATITIS IN EXPERIMENTALLY INFECTED PUPPIES

Infectious canine hepatitis (ICH) is a systemic disease of Canidae and Ursidae caused by canine adenovirus type 1 (CAV-1) produces acute necrohemorrhagic hepatitis. The aim of the present study was to throw the light on the humoral and molecular diagnosis by polymerase chain reaction (PCR) and biochemical changes that occur in puppies infected with infectious canine hepatitis virus. Liver functions. tests, hematological profile, in addition to histopathological changes were performed. The study was carried out on fourteen native breed puppies of about three to four months old, apparently healthy, free from internal and external parasites. They were fed balanced diet and adequate water and housed under hygienic conditions in special isolated kennels. The animals were not vaccinated, and found to be free from canine hepatitis antibodies as screened by serum neutralization test. Puppies were divided into two groups, group 1, composed of 11 puppies were experimentally infected group with ICHV, and group 2, composed of 3 puppies were kept as non- infected control group. The results showed that, CAV-1 was detected in eight infected puppies by PCR showing amplicon of 508 bp sizes at the 1st and 2nd week post viral infection. The infected puppies showed an elevation of serum enzymes activities as ALT, AST, ALP and GGT throughout the experimental period, also serum total protein and serum albumin were decreased at the 3rd and 4th week post infection. Concerning hematological profile the infected puppies showed a decrease of HB, RBCs, platelets and haematocrit throughout the experimental period leading to anemia. The infected puppies showed a decrease of the total leukocytic count throughout the experimental period whereas neutrophils count increased significantly at the 1st week post viral infection then decline to the normal level at the 2nd week and finally decreased below the normal upper limits at the 3rd and 4th weeks. The infected puppies showed a decrease of lymphocytes count at 1st week post viral infection and then rapidly increased at the 3rd and 4th week post viral infection. Moreover, the mean values of monocytes and eosinophils count increased gradually throughout the experimental period. It was clearly observed from the present study that, PCR procedure is faster, sensitive and easier as diagnostic biomarkers for ICH especially at the acute stage. Moreover, liver functions tests as well as hematological indices were the best diagnostic biomarkers in the chronic stage of ICH.

Antimicrobial Profile of Selected Snake Venoms and Their Associated Enzymatic Activities

Aims: To investigate the antiviral and antibacterial profile of several crude snake venoms and to assess some of their enzymatic activities. Methodology: The antiviral activities of Naja haje, Bitis arietans, Naja nigricollis and Echis carinatus snake venoms were investigated against Herpes simplex virus type1, Rift valley fever virus and Vesicular stomatitis virus using the end point of cytopathic effect method. Antibacterial activities of Bitis arietans, Cerastes cerastes, Echis carinatus, Vipera lebetina, Naja naja, Pseudechis australis, Naja nigricollis and Naja haje venoms were examined against Staphylococcus aureus, Escherichia coli, Salmonella typhimurium and Pseudomonas aeruginosa using disc diffusion method. Microdilution method was used to determine the venom's minimum inhibitory concentration. L-amino acid oxidase and phospholipase A2 activities of crude venoms were evaluated using enzymatic assays. Results: Naja nigricollis, Bitis arietans and Echis carinatus snake venoms exhibited significant antiviral activities against all test viruses, except for N. haje treated cells. The mean depletion of viral infectivity titer of venom pretreated cells was higher than its depletion post viral infection for all three venoms showing antiviral activities. Naja nigricollis exhibited the highest antiviral activity against test viruses and recorded a mean depletion of viral infectivity titer in venom pretreated cells of 3.8 log (10) / ml , 3.2 log (10) / ml and 2.5 Research Article British Microbiology Research Journal, 2(4): 251-263, 2012 252 log (10) / ml for HSV-1, RVFV and VSV, respectively. Pseudechis australis, followed by Naja naja and Naja nigricollis venoms, showed the highest inhibitory activity against test bacteria with inhibition zones ranging from 11-17 mm, 8-14 mm and 8-13 mm, respectively. Minimum inhibitory concentrations of test venoms against different bacterial strains ranged from 156 μg / ml to 1.25 mg / ml. Maximum Lamino oxidase activity was detected in Naja naja, Cerastes cerastes and Pseudechis australis. The highest Phospholipase A2 activity was identified in Bitis arietans, Pseudechis australis, Naja naja and Naja nigricollis. Conclusion: It can be concluded that snake venoms or their bioactive derivatives can be promising therapeutic agents against some microbial infections. Further investigations will be carried out for purification and more characterization of the biologically active components in snake venoms.

Mutagenesis of Surfactant Protein D Informed by Evolution and X-ray Crystallography Enhances Defenses against Influenza A Virus in Vivo

The recognition of influenza A virus (IAV) by surfactant protein D (SP-D) is mediated by interactions between the SP-D carbohydrate recognition domains (CRD) and glycans displayed on envelope glycoproteins. Although native human SP-D shows potent antiviral and aggregating activity, trimeric recombinant neck+CRDs (NCRDs) show little or no capacity to influence IAV infection. A mutant trimeric NCRD, D325A/R343V, showed marked hemagglutination inhibition and viral neutralization, with viral aggregation and aggregation-dependent viral uptake by neutrophils. D325A/R343V exhibited glucose-sensitive binding to Phil82 hemagglutinin trimer (HA) by surface plasmon resonance. By contrast, there was very low binding to the HA trimer from another virus (PR8) that lacks glycans on the HA head. Mass spectrometry demonstrated the presence of high mannose glycans on the Phil82 HA at positions known to contribute to IAV binding. Molecular modeling predicted an enhanced capacity for bridging interactions between HA glycans and D325A/R343V. Finally, the trimeric D325A/R343V NCRD decreased morbidity and increased viral clearance in a murine model of IAV infection using a reassortant A/WSN/33 virus with a more heavily glycosylated HA. The combined data support a model in which altered binding by a truncated mutant SP-D to IAV HA glycans facilitates viral aggregation, leading to significant viral neutralization in vitro and in vivo. These studies demonstrate the potential utility of homology modeling and protein structure analysis for engineering effective collectin antivirals as in vivo therapeutics.

2A Peptide-based, Lentivirus-mediated Anti-death Receptor 5 Chimeric Antibody Expression Prevents Tumor Growth in Nude Mice

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, induces tumor cell death via death receptors on target cells, without adverse effects on most normal cells. Its receptors are therefore an attractive target for antibody-mediated tumor therapy. Here, we report the creation of a lentivirus vector constructed by linking the heavy chain and the light chain of the antibody with a 2A/furin self-processing peptide in a single open reading frame that expresses a novel chimeric antibody (named as zaptuximab) with tumoricidal activity, which is consisted of the variable region of a mouse anti-human DR5 monoclonal antibody, AD5-10, and the constant region of human immunoglobulin G1. Lentivirus-expressed zaptuximab bound specifically to its antigen, DR5, and exhibited significant apoptosis-inducing activity in various tumor cell lines. The packaged recombinant virus lenti-HF2AL showed strong apoptosis-inducing activity in vitro. Meanwhile, inoculated subcutaneous human colon HCT116 tumor formation in nude mice were inhibited significantly. Moreover, there was a synergistic effect of mitomycin C (MMC) on the observed tumoricidal efficacy, prolonging the life span of nude mice with orthotopic human lung tumor cancers. These data suggest that lentivirus-mediated, 2A peptide-based anti-DR5 chimeric antibody expression may have clinical utility as an anticancer treatment and may represent a rational adjuvant therapy in combination with chemotherapy.

Infection with human coronavirus NL63 enhances streptococcal adherence to epithelial cells.

Understanding the mechanisms of augmented bacterial pathogenicity in post-viral infections is the first step in the development of an effective therapy. This study assessed the effect of human coronavirus NL63 (HCoV-NL63) on the adherence of bacterial pathogens associated with respiratory tract illnesses. It was shown that HCoV-NL63 infection resulted in an increased adherence of Streptococcus pneumoniae to virus-infected cell lines and fully differentiated primary human airway epithelium cultures. The enhanced binding of bacteria correlated with an increased expression level of the platelet-activating factor receptor (PAF-R), but detailed evaluation of the bacterium-PAF-R interaction revealed a limited relevance of this process.

The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection

Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained viral response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is expensive, prolonged, and associated with serious side-effects. Evidence suggests that a poor response to treatment may be the result of a suppressed anti-viral immunity due to the presence of increased numbers and activity of CD4+CD25+Foxp3+ regulatory T cells (Treg cells). We and others have recently identified fibrinogen-like protein 2 (FGL2) as a putative effector of Treg cells, which accounts for their suppressive function through binding to Fc gamma receptors (FcγR). In an experimental model of fulminant viral hepatitis, our laboratory showed that increased plasma levels of FGL2 pre- and post-viral infection were predictive of susceptibility and severity of disease. Moreover, treatment with antibody to FGL2 fully protected susceptible animals from the lethality of the virus, and adoptive transfer of wild-type Treg cells into resistant fgl2-deficient animals accelerated their mortality post-infection. In patients with HCV infection, plasma levels of FGL2 and expression of FGL2 in the liver correlated with the course and severity of the disease. Collectively, these studies suggest that FGL2 may be used as a biomarker to predict disease progression in HCV patients and be a logical target for the development of novel therapeutic approaches for the treatment of patients with HCV infection.

The online Cough Clinic

To the Editors: The recent paper by Dettmar et al. 1 describes an important way in which patients with chronic cough (and their general practitioners) can obtain information online as to the probable diagnosis of their coughs and the preferred treatment. The only three possible diagnoses are reflux (gastro-oesophageal reflux (GOR)), asthma and rhinitis (post-nasal drip syndrome (PNDS)). We tested the questionnaire with histories of four patients. They had respectively post-viral, cigarette smoking, habit (Tourette's) and upper respiratory tract infection cough. Each was diagnosed as probable GOR. The paper raises a number of important questions. First, the paper lists 16 questions pointing to the probable diagnoses, which are identified for each question. However, the current online questionnaire (November 2009) adds a further five questions with no indication of the diagnoses they point to, surely essential information. Presumably this change in the questionnaire was made after the paper was submitted, but it means that the results described in the paper cannot be added to any results from the “new” online questionnaire. Secondly, how “specific” are the questions? For …

Biomarkers for Prediction of Bovine Respiratory Disease Outcome

Fatal bovine respiratory disease (BRD) is frequently the result of a primary viral and a secondary bacterial respiratory infection. In cattle, BRD causes more than half of feedlot deaths and has a major impact on financial losses in the cattle industry in North America. It is, therefore, very important to understand the mechanism of this complex disease process as well to predict and identify BRD susceptible cattle to enhance treatment efficacy. We recently established the value of using combinatorial omics approaches to identify candidate biomarkers associated with stress responses, a factor that can increase the severity of BRD. The objective of the present investigation was to experimentally recreate fatal BRD and to use a combinatorial analysis of proteomic, metabonomic, and elemental profiles in serum samples to determine if multimethod analysis of these biomarkers could predict disease outcome. The proteomic studies revealed that changes in the serum proteome were significant on day 4 postviral infection when compared to preinfection (day 0) serum samples. Proteomic studies identified a group of acute phase proteins (haptoglobin and apolipoprotein AI), which could be linked to a primary viral respiratory infection, but there was no significant association observed with fatal BRD. In contrast, metabonomic and elemental analyses identified candidate biomarkers for viral infection (glucose, LDL, valine, phosphorous, and iron) and disease outcome (lactate, glucose, iron). While multivariate analysis of proteomic and metabolite profiles did not discriminate between animals that survived or died postsynergic viral-bacterial infection by analyzing preinfection (day 0) serum samples, analysis of serum elemental profiles prior to infection was, however, predictive of BRD outcome. Furthermore, discriminant analyses of all three methodologies used to profile serum (collected on day 4 postviral but prior to bacterial infection) revealed differential trends between animals that survived or died following synergic viral-bacterial infection. Thus, a combinatorial approach using proteomic, metabonomic, and elemental analyses of serum samples revealed that multimethod analysis could discriminate between the complex biological responses to secondary bacterial respiratory infection and predict disease outcome.

Lyme Disease Presenting with Gastroparesis and Cranial Nerve Vii Palsy

Purpose: A previously healthy 62-year-old male from Eastern Pennsylvania was admitted to the hospital with 10 weeks of “band-like” upper abdominal pain associated with nausea, constipation, post-prandial bloating, early satiety and a 30-lb weight loss. These symptoms were preceded by an ovoid, non-pruritic, non-vesicular rash on his right gluteus maximus that spontaneously resolved in 2 weeks. A prior extensive workup including upper and lower endoscopy, abdominopelvic CT, and MRI/MRA, small bowel series, and abdominal ultrasound was unrevealing. Supportive medications included tramadol, hydromorphone, colace, polyethylene glycol, and zolpidem. Physical exam on admission was significant for mild epigastric abdominal tenderness. Laboratory testing revealed an elevated ALT of 53 IU/L (normal <45) and CRP of 1.4 mg/dL (normal <0.80). A gastric emptying scan was performed with an emptying half time of 490 minutes (significantly delayed). On hospital day 2, the patient developed a left-sided facial droop. Brain MRI was normal. Lumbar puncture revealed a lymphocytosis, elevated protein, and elevated Lyme IgG titers. Elevated serum Lyme antibody was confirmed by Western blot. The patient was diagnosed with early-disseminated Lyme disease, complicated by cranial nerve VII palsy and gastroparesis. Ceftriaxone was initiated and continued for 4 weeks at home; a gastroparesis diet and metoclopramide were started. At follow-up 3 weeks later, the patient's symptoms were markedly diminished, and he had gained 5 lbs. Two months after discharge, the patient was asymptomatic except for a slight left-sided facial droop; a repeat gastric emptying scan was normal. Gastroparesis is a chronic disorder of delayed gastric emptying without mechanical obstruction. The most common etiologies are diabetes, post-surgical and idiopathic; a subset of the latter category may be associated with post-viral infections. Lyme disease is the most common tick-borne disease in the U.S. and is caused by the spirochete Borrelia burgdorferi, which can elicit a multisystem inflammatory response and is often accompanied by the hallmark rash, erythema migrans. The most common gastrointestinal symptom of Lyme disease is subclinical hepatitis, although dysmotility syndromes including gastroparesis and intestinal pseudo-obstruction have been reported. While the pathogenesis is not completely understood, gastroparesis secondary to Lyme disease may result from an inflammatory neuropathy of the enteric nervous system by direct invasion of B. burgdorferi or an indirect, cell-mediated inflammatory response. This case highlights an unusual presentation of a relatively common (regional) disease.

Effective Treatment of Smell Loss with Theophylline

While patients with smell loss in the US number in the millions there has been no effective method to either evaluate or treat the majority of them. These patients exhibit several causes for their loss including post viral infection, head injury and allergic rhinitis. Their semll loss has been measured objectively by psychophysical techniques and subjectively by quantitative evaluation of loss. We described the major biochemical defect causing these sensory losses‐decreased cAMP and cGMP in nasal mucus; this defect inhibits growth and development of olfactory receptor cells. To improve patients’ sensory loss we attempted to correct their observed biochemical defect by increasing cAMP and cGMP though use of the phosphodiesterase inhibitor theophylline which we gave orally to 309 patients at doses of 200–600 mg for 2–8 months. Psychophysical measurements of smell function improved in over 70%. Subjective responses improved in only 144 (47%); among these responders were 27% who improved 51% and 20% who improved 84%. 165 (53%) did not improve‐nonresponders‐ who improved 0.5%. Responders had significantly less severe smell loss than did nonresponders but there were no differences in age or blood levels of theophylline. These results indicate that patients with smell loss of several etiologies with this biochemical defect can be treated effectively with theophylline to improve smell fucntion.

Nerve growth factor and tissue repair remodeling: trkA NGFR and p75 NTR, two receptors one fate

This review deals with the role of nerve growth factor (NGF) in healing process as a result of injury. The role of both trkA NGFR and p75 NTR specific NGF receptors and their contribution in the complex network of tissue repair process, is discussed and highlighted in view of recent findings. In fact, NGF represents a significant advance in the treatment of etiologically different ulcers (corneal ulcers, pressure ulcers, post-viral infections, chemical burns) and might shorten the recovery process. For these diseases, no specific treatment is actually available. It is reasonable that apart from NGF and/or neurotrophins a different time-course of trkA NGRF/p75 NTR expression, might regulate the final process. In summary, these novel findings on the potential pro-healing capacity of NGF might open new possibilities for this growth factor in modulating the healing processes in several pathological conditions.