Alpha-1 Antitrypsin Therapy Modifies Neutrophil Adhesion in Patients with Obstructive Lung Disease.

Alpha-1 antitrypsin deficiency (AATD) is characterized by neutrophil-dominated inflammation resulting in emphysema. The cholesterol-rich neutrophil outer plasma membrane plays a central role in adhesion and subsequent transmigration to underlying tissues. This study aimed to investigate mechanisms of increased neutrophil adhesion in AATD and whether alpha-1 antitrypsin (AAT) augmentation therapy abrogates this effect. Plasma and blood neutrophils were donated by healthy controls (n = 20), AATD (n = 30), and AATD patients after AAT augmentation therapy (n = 6). Neutrophil membrane protein expression was investigated using liquid chromatography-tandem mass spectrometry. The effect of once-weekly intravenous AAT augmentation therapy was assessed by calcium fluorometric, µ-calpain, and cell adhesion assays. Decreased neutrophil plasma membrane cholesterol content (P = 0.03), yet increased abundance of integrin α-M (fold change 1.91), integrin α-L (fold change 3.76), and cytoskeletal adaptor proteins including talin-1 (fold change 4.04) were detected on AATD neutrophil plasma membrane fractions. The described inflammatory induced structural changes were a result of a more than twofold increased cytosolic calcium concentration (P = 0.02), leading to significant calcium-dependent µ-calpain activity (3.5-fold change; P = 0.005), resulting in proteolysis of the membrane cholesterol trafficking protein caveolin-1. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased caveolin-1 and membrane cholesterol content (111.8 ± 15.5 vs. 64.18 ± 7.8 µg/2 × 107 cells before and after treatment, respectively; P = 0.02), with concurrent decreased neutrophil integrin expression and adhesion. Results demonstrate an auxiliary benefit of AAT augmentation therapy, evident by a decrease in circulating inflammation and controlled neutrophil adhesion.

Seroprevalence of Bluetongue Virus in small ruminants in Balochistan province, Pakistan.

Bluetongue (BT), caused by bluetongue virus (BTV), is a vector-borne disease of small ruminants that has the potential to spread across international borders. Despite large populations of susceptible animals and borders with BTV endemic countries, little is known of the disease burden and prevalent serotypes in the province of Balochistan in Pakistan. We conducted a cross-sectional study to determine seroconversion and prevalent serotypes in selected districts of the province using a competitive enzyme-linked immunosorbent assay (cELISA) and real-time polymerase chain reaction (RT-PCR). Sera (n = 876) were collected from clinically healthy sheep and goats originating from the districts of Quetta (n = 300), Mastung (n = 201), Killa Saifullah (n = 75) and Kech (n = 300). None of the study herds (n = 97) were seronegative for BTV, and at the individual level, the overall prevalence of BTV seroconversion was 47.26% (n = 414/876, 95% CI = 43.92%-50.63%). A higher percentage of goats (50.87%, 95% CI = 45.99%-55.73%) were seropositive for anti-VP7 immunoglobulins (IgG) than sheep (44.21%, 95% CI = 39.81%-48.70%). Odds ratios of seroconversion for goats were associated with breed type (χ2  = 16.84, p = .01), parity (χ2  = 23.66, p = .00) and presence of vector (χ2  = 2.63, p = .10), whereas for sheep, it was associated with breed type (χ2  = 13.80, p = .01) and parity (χ2  = 53.40, p = .00). Serotype 8 was the most prevalent (26.82%, 95% CI = 14.75%-43.21%) followed by an equal prevalence of serotypes 2 and 9 (7.31%, 95% CI = 1.91%-21.01%). To the best of our knowledge, this is the first study conducted in Balochistan province and the results indicate that there is a necessity to initiate intervention strategies to control BT disease burden not only in this region of Pakistan but also in adjacent areas of the neighbouring countries, Iran and Afghanistan.

Some challenges to progressive control of foot and mouth disease in Pakistan--findings of a pilot survey.

Pakistan is at an initial stage for progressive control of foot and mouth disease (FMD). Understanding the risk factors for introduction, spread and persistence of the infection is important to design an evidence-based disease control programme. A rapid appraisal method was adopted, and a convenient sample of twenty commercial dairy farmers was interviewed. The following were considered to contribute in secondary transmission of infection: (i) intermediaries and service providers [animal health workers, animal traders and transporters, raw milk collectors, persons who remove skin of dead animals], (ii) places where animals come in close contact [livestock markets, animal fairs, communal grazing pastures, routes in villages where livestock move, watering points, animal transport vehicles], (iii) use of bulls immediately after recovery from FMD infection, (iv) range land/desert livestock production, (v) small holder sheep and goat production, (vi) purchase of replacement stock and fodder from infected locations. This article reveals contacts within and between villages, some of which may act as routes of transmission of FMD. The study suggests the need for zoosanitary education of the livestock keepers.

Pelvic primary staphylococcal infection presenting as a thigh abscess.

Intra-abdominal disease can present as an extra-abdominal abscess and can follow several routes, including the greater sciatic foramen, obturator foramen, femoral canal, pelvic outlet, and inguinal canal. Nerves and vessels can also serve as a route out of the abdomen. The psoas muscle extends from the twelfth thoracic and fifth lower lumbar vertebrae to the lesser trochanter of the femur, which means that disease in this muscle group can migrate along the muscle, out of the abdomen, and present as a thigh abscess. We present a case of a primary pelvic staphylococcal infection presenting as a thigh abscess. The patient was a 60-year-old man who presented with left posterior thigh pain and fever. Physical examination revealed a diffusely swollen left thigh with overlying erythematous, shiny, and tense skin. X-rays revealed no significant soft tissue lesions, ultrasound was suggestive of an inflammatory process, and MRI showed inflammatory changes along the left hemipelvis and thigh involving the iliacus muscle group, left gluteal region, and obturator internus muscle. The abscess was drained passively via two incisions in the posterior left thigh, releasing large amounts of purulent discharge. Subsequent bacterial culture revealed profuse growth of Staphylococcus aureus. The patient recovered uneventfully except for a moderate fever on the third postoperative day.

Prevalence, hematology, and treatment of balantidiasis among donkeys in and around Lahore, Pakistan.

The prevalence of Balantidium coli among donkeys in Lahore and adjoining areas was surveyed and a trial conducted to determine the efficacy of two antiprotozoal drugs: secnidazole (Dysen Forte) and Kalonji (Nigella sativa). Four-hundred donkeys were examined, and 73 (18.3%) were found positive for Balantidium coli. A slight decrease in PCV and an increase in Hb values of infected donkeys were found after antiprotozoal treatment. Secnidazole was 89.5% effective for the treatment of equine balantidiasis compared to 40.0% for Nigella sativa. This is the first report of balantidiasis in equines from Pakistan. It is not known if balantidiasis is an emerging problem in equines or whether it is a newly reported infection.

Orbital hydatid cyst.

Hydatid cysts rarely appear isolated in the orbital cavity without involvement of other organs. Most of these are situated in the superolateral and superomedial angles of the orbit. Inferiorly located cysts are very uncommon. The authors report a case of a primary hydatid cyst of the orbit with inferiolateral localization. The cyst was enucleated surgically via a rhinotomy approach. This case was considered as a primary infection, because there was no previous history of hydatid disease and no findings of liver and lung cysts on radiological examination. Physicians should include orbital hydatid cyst in the differential diagnosis of unilateral proptosis. To avoid complications that might occur during surgery, the cyst can be easily removed using a gentile enucleation technique.

Have neonatal mortality rates in the state of Qatar become static? A PEARL study analysis.

To ascertain the national neonatal mortality rate in Qatar during the first quarter of 2011 (1 January-31 March), we carried out a prospective pilot national epidemiologic study. Nationwide birth and neonatal mortality data were collected using predesigned, structured questionnaires. To analyse trends over the previous 4 years (2008-2011) we used neonatal mortality data for 2008-2010 from the database of the neonatal unit at the Women's Hospital, annual reports of Hamad Medical Corporation, and published neonatal mortality data for 2010 for comparative analysis. A total of 4909 live births and 21 neonatal deaths were recorded during the study period. The neonatal mortality rate was 4.28/1000 live births (corrected neonatal mortality rate 2.85/1000). The early neonatal mortality rate was 1.84/1000 and the late neonatal mortality rate was 2.44/1000 live births. Fifteen of the 21 neonatal deaths were in non-Qatari babies, reflecting the ethnic distribution in the population. Neonatal mortality rates in Qatar declined very little between 2008 and the first quarter of 2011.

Have neonatal mortality rates in the state of Qatar become static? A PEARL study analysis

To ascertain the national neonatal mortality rate in Qatar during the first quarter of 2011 [1 January-31 March], we carried out a prospective pilot national epidemiologic study. Nationwide birth and neonatal mortality data were collected using predesigned, structured questionnaires. To analyse trends over the previous 4 years [2008-2011] we used neonatal mortality data for 2008-2010 from the database of the neonatal unit at the Women's Hospital, annual reports of Hamad Medical Corporation, and published neonatal mortality data for 2010 for comparative analysis. A total of 4909 live births and 21 neonatal deaths were recorded during the study period. The neonatal mortality rate was 4.28 /1000 live births [corrected neonatal mortality rate 2.85 /1000]. The early neonatal mortality rate was 1.84 /1000 and the late neonatal mortality rate was 2.44/1000 live births. Fifteen of the 21 neonatal deaths were in non-Qatari babies, reflecting the ethnic distribution in the population. Neonatal mortality rates in Qatar declined very little between 2008 and the first quarter of 2011

Copper status in breeding and racing camels (Camelus dromedarius) and response to cupric oxide needle capsules.

Copper was determined in the blood of breeding camels, camel calves and racing camels to evaluate copper status in these animals in UAE. Low blood copper concentrations were reported in newly born camel calves (100%) and calves 2-4 months old (68%), breeding camels at early (55.6%) and at mid lactation (48%) and at late pregnancy (69%). This is attributed to the low copper and high sulfate in the Rhodes grass which is the only diet offered to the breeding camels. On the other hand only 9.7% of racing camels showed low copper levels. This is because copper is routinely offered to racing camels when their blood copper is low. Cupric oxide needle capsules orally administered at the rate of 8 g per adult camel was effective in elevating blood copper from 7.083 micromol/L at day zero to 10.074 micromol/L at day 28 after dosing.

Retinol values in the plasma of the Arabian camel (Camelus dromedarius) and the influence of aflatoxicosis.

The normal values are reported of the concentration of vitamin A (retinol) in the plasma of 44 male and female adult camels (Camelus dromedarius) in the United Arab Emirates. The concentrations of the vitamin in the plasma of eight camels of both sexes afflicted with aflatoxicosis were also determined. The mean concentration (+/-SD) of the vitamin in healthy camels was 460.1 +/- 49.3 ng/L. Sex had no significant effect on the concentration of the vitamin. Camels with aflatoxicosis had a mean concentration of retinol in the plasma of 243.4 +/- 32.3 ng/L. The concentrations of aflatoxins in the liver and ruminal contents of these animals were 18.2 +/- 1.3 and 243.4 microg/kg, respectively.

Novel tumor-promoting property of tamoxifen.

The tumor-promoting phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) cooperates with c-Src overexpression to transform rat fibroblasts. TPA transforms c-Src-overexpressing cells by depleting the delta isoform of protein kinase C (PKCdelta). Tamoxifen, which has both estrogen-mimetic and estrogen-antagonist properties, has been widely used to improve the prognosis of breast cancer patients. However, with extended use, there is an increased risk for endometrial and other cancers that can be observed within 10 years of treatment. We report here that tamoxifen, similar to TPA, cooperates with c-Src overexpression to transform 3Y1 rat fibroblasts. Tamoxifen induced both DNA synthesis and anchorage-independent cell proliferation in c-Src-overexpressing, but not in parental, 3Y1 rat fibroblasts. Tamoxifen also induced an association between c-Src and PKCdelta that resulted in the tyrosine phosphorylation and down-regulation of PKCdelta. These phenotypes were not induced by estrogen, indicating that the effect of tamoxifen was in addition to any estrogen-mimetic effects. Thus, in addition to the hyperplasia-inducing capability of an estrogen-mimetic, tamoxifen has an additional tumor-promoting capability similar to that of TPA. The dual tumor-promoting capability of both estrogen- and TPA-mimetic properties for tamoxifen may contribute to the increased incidence of endometrial cancers observed in the relatively short exposure period of <10 years.