Seroepizootiological investigation on Goat Warble Fly Infestation (Przhevalskiana silenus) in Pothwar Plateau, Pakistan.

Goat Warble Fly Infestation (GWFI) is also known as subcutaneous myiasis caused by Przhevalskiana silenus (Diptera: Oestridae). It is widely distributed in tropical and sub-tropical areas of the world. In goats, WFI is usually detected through conventional procedure which underestimated the infestation. The current study was designed to determine the serodiagonsis of GWFI (through IDEXX Hypodermosis serum antibody test) and also aimed to investigate its seroepizootiological profile in Pothwar region, Pakistan from 2013-14. The results showed that average seropositivity (ELISA kit) of GWFI was 18.5% whereas, it was 11% by using conventional procedure (Palpation method) depicting a significant difference (p<0.05). Higher seropositivity (30.8%) was observed in Jhelum district as compared to e Attock district (6%). The L1 larvae were found in September, while nodules start appearing in October to December and last until the end of February. The month wise peaks of optical density (OD) was higher in December which gradually decrease along with the end of winter season. The prevalence of GWFI revealed no significant difference among three host breeds (Jattal, Beetal and Tedy). According to the results, high infestation rate (28%) was observed in young animals of age group < 1 year as compared to old animals (> 2 years). Topographically, hilly areas (33%) provide favourable climatic conditions for the propagating of larval stages. Sex difference showed no significant difference. The seroprevalence varied significantly with respect to age, month, districts and topographical location. The current study proved that serologic diagnosis (commercial ELISA kit) as more sensitive and accurate for timely diagnosis of GWFI than traditional method. The information on the epizootiology of P. silenus in goats of Pothwar region would help in devising effective control strategies.

Seroepizootiological investigation on Goat Warble Fly Infestation (Przhevalskiana silenus) in Pothwar Plateau, Pakistan

@#Goat Warble Fly Infestation (GWFI) is also known as subcutaneous myiasis caused by Przhevalskiana silenus (Diptera: Oestridae). It is widely distributed in tropical and sub-tropical areas of the world. In goats, WFI is usually detected through conventional procedure which underestimated the infestation. The current study was designed to determine the serodiagonsis of GWFI (through IDEXX Hypodermosis serum antibody test) and also aimed to investigate its seroepizootiological profile in Pothwar region, Pakistan from 2013-14. The results showed that average seropositivity (ELISA kit) of GWFI was 18.5% whereas, it was 11% by using conventional procedure (Palpation method) depicting a significant difference (p<0.05). Higher seropositivity (30.8%) was observed in Jhelum district as compared to e Attock district (6%). The L1 larvae were found in September, while nodules start appearing in October to December and last until the end of February. The month wise peaks of optical density (OD) was higher in December which gradually decrease along with the end of winter season. The prevalence of GWFI revealed no significant difference among three host breeds (Jattal, Beetal and Tedy). According to the results, high infestation rate (28%) was observed in young animals of age group < 1 year as compared to old animals (> 2 years). Topographically, hilly areas (33%) provide favourable climatic conditions for the propagating of larval stages. Sex difference showed no significant difference. The seroprevalence varied significantly with respect to age, month, districts and topographical location. The current study proved that serologic diagnosis (commercial ELISA kit) as more sensitive and accurate for timely diagnosis of GWFI than traditional method. The information on the epizootiology of P. silenus in goats of Pothwar region would help in devising effective control strategies.

Up in smoke: An unusual case of diffuse alveolar hemorrhage from marijuana.

Diffuse alveolar hemorrhage (DAH) can be a serious and life threating condition. Illicit substance use has been associated with DAH, with cocaine being the most widely reported. Marijuana use has been associated with pulmonary complications in the form of pneumomediatsium, pneumothorax, bullous disease, and pulmonary aspergillosis. We present a case of diffuse alveolar hemorrhage (DAH) resulting from marijuana inhalation, a finding rarely described in the literature. A 21-year-old male presented with several episodes of hemoptysis after drinking alcohol and smoking marijuana. He reported smoking 5-8 joints per day of marijuana (he denied use of bongs or other inhalant aids). His respiratory exam revealed bilateral fine rales. Laboratory evaluation included leukocytosis with left shift, normal platelets, coagulation profile, and a urine toxicology screen positive for tetrahydocanabinoid (THC). Chest CT revealed bilateral diffuse alveolar infiltrates suggestive of DAH. A bronchoscopy with BAL of bilateral upper lobes consistent with DAH with negative microbiologic studies, hemosiderin laden macrophages were present. Additional workup included a normal Echocardiogram, negative autoimmune serologies. His hemoptysis resolved with supportive care. DAH is a potentially fatal disease that has been associated with illicit substance use, most commonly cocaine. Recently, reports have surfaced associating marijuana use with DAH, though these cases have all involved the use of bongs or other inhalant aids, leading to the hypothesis that combustibles and inhaled particles may be the etiologic factor. This is the second report of DAH developing after smoking only marijuana, though the etiology for the association between marijuana use and DAH remains uncertain.

PET-CT imaging in patients with chronic sternal wound infections prior to reconstructive surgery: A case series.

Late presenting and recurrent sternal wound infections post-sternotomy are difficult to treat, with the clinical picture not necessarily reflecting the underlying problem. As a result of our experience, we suggest that these chronic cases should be managed using a different algorithm to acute sternal wound infection. Positron emission tomography combined with computerized tomography (PET-CT) imaging may be potentially useful in enabling accurate localization of disease sites, which guides adequate debridement prior to definitive reconstruction. It may also allow for disease surveillance and monitoring of the response to antimicrobial treatment. We present three cases which support the need for pre-operative imaging using PET-CT.

Erratum to: Thrombospondin 1 is a key mediator of transforming growth factor b-mediated cell contractility in systemic sclerosis via a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent mechanism.

[This corrects the article DOI: 10.1186/1755-1536-4-9.].

Isometric contraction of Dupuytren's myofibroblasts is inhibited by blocking intercellular junctions.

Myofibroblasts (MFs) are responsible for both physiological wound and scar contraction. However, it is not known whether these cells act individually to contract the surrounding matrix or whether they behave in a coordinated manner. Therefore, we studied intercellular junctions of primary human MFs derived from patients with Dupuytren's disease, a fibrotic disorder of the dermis and subdermal tissues of the palm. The cells were maintained in anchored three-dimensional collagen lattices to closely mimic conditions in vivo. We found that selective blockade of adherens, mechanosensitive, or gap junctions effectively inhibited contraction of the collagen matrices and downregulated the MF phenotype. Our data indicate that MFs in part function as a coordinated cellular syncytium, and disruption of intercellular communication may provide a therapeutic target in diseases characterized by an overabundance of these contractile cells.

Unraveling the signaling pathways promoting fibrosis in Dupuytren's disease reveals TNF as a therapeutic target.

Dupuytren's disease is a very common progressive fibrosis of the palm leading to flexion deformities of the digits that impair hand function. The cell responsible for development of the disease is the myofibroblast. There is currently no treatment for early disease or for preventing recurrence following surgical excision of affected tissue in advanced disease. Therefore, we sought to unravel the signaling pathways leading to the development of myofibroblasts in Dupuytren's disease. We characterized the cells present in Dupuytren's tissue and found significant numbers of immune cells, including classically activated macrophages. High levels of proinflammatory cytokines were also detected in tissue from Dupuytren's patients. We compared the effects of these cytokines on contraction and profibrotic signaling pathways in fibroblasts from the palmar and nonpalmar dermis of Dupuytren's patients and palmar fibroblasts from non-Dupuytren's patients. Exogenous addition of TNF, but not other cytokines, including IL-6 and IL-1ß, promoted differentiation into specifically of palmar dermal fibroblasts from Dupuytren's patients in to myofibroblasts. We also demonstrated that TNF acts via the Wnt signaling pathway to drive contraction and profibrotic signaling in these cells. Finally, we examined the effects of targeted cytokine inhibition. Neutralizing antibodies to TNF inhibited the contractile activity of myofibroblasts derived from Dupuytren's patients, reduced their expression of α-smooth muscle actin, and mediated disassembly of the contractile apparatus. Therefore, we showed that localized inflammation in Dupuytren's disease contributes to the development and progression of this fibroproliferative disorder and identified TNF as a therapeutic target to down-regulate myofibroblast differentiation and activity.

Thrombospondin 1 is a key mediator of transforming growth factor ß-mediated cell contractility in systemic sclerosis via a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent mechanism.

BACKGROUND: The mechanism underlying the ability of fibroblasts to contract a collagen gel matrix is largely unknown. Fibroblasts from scarred (lesional) areas of patients with the fibrotic disease scleroderma show enhanced ability to contract collagen relative to healthy fibroblasts. Thrombospondin 1 (TSP1), an activator of latent transforming growth factor (TGF)ß, is overexpressed by scleroderma fibroblasts. In this report we investigate whether activation of latent TGFß by TSP1 plays a key role in matrix contraction by normal and scleroderma fibroblasts. METHODS: We use the fibroblast populated collagen lattices (FPCL) model of matrix contraction to show that interfering with TSP1/TGFß binding and knockdown of TSP1 expression suppressed the contractile ability of normal and scleroderma fibroblasts basally and in response to TGFß. Previously, we have shown that ras/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) mediates matrix contraction basally and in response to TGFß. RESULTS: During mechanical stimulation in the FPCL system, using a multistation tensioning-culture force monitor (mst-CFM), TSP1 expression and p-ERK activation in fibroblasts are enhanced. Inhibiting TSP1 activity reduced the elevated activation of MEK/ERK and expression of key fibrogenic proteins. TSP1 also blocked platelet-derived growth factor (PDGF)-induced contractile activity and MEK/ERK activation. CONCLUSIONS: TSP1 is a key mediator of matrix contraction of normal and systemic sclerosis fibroblasts, via MEK/ERK.