Bovine immunoglobulin concentrate-Clostridium difficile retains C difficile toxin neutralising activity after passage through the human stomach and small intestine

Background—Bovine immunoglobulinconcentrate (BIC)-Clostridium difficile isprepared from the colostrum of cows immunised against C difficile toxins and contains highconcentrations of neutralising IgG antitoxin.
Aims—To determine the proportion ofBIC-C difficile which survives passagethrough the human stomach and small intestine.
Methods—Six volunteers with an endileostomy took 5 g of BIC-C difficilecontaining 2.1 g of bovine IgG on four occasions: alone, with anantacid, during treatment with omeprazole, and within enteric coated capsules.
Results—WhenBIC-C difficile was taken alone, a mean (SEM) of 1033 (232) mg of bovine IgG was recovered in the ileal fluidrepresenting 49% of the total ingested dose. Bovine IgG recovery wasnot significantly increased by antacid (636 (129) mg) or omeprazole(1052 (268) mg). The enteric capsules frequently remained intact oronly partially opened in the ileal effluent and free bovine IgG levelswere low in this treatment group (89(101) mg). Bovine IgG recovery washigher in volunteers with shorter (less than two hours) mouth to ileumtransit times (68% versus 36%, p<0.05). Specific bovine IgG againstC difficile toxin A was detected in ilealfluid following oral BIC. Toxin neutralising activity was also presentand correlated closely with bovine IgG levels(r=0.95, p<0.001).
Conclusion—BIC-Cdifficile resists digestion in the human upper gastrointestinaltract and specific anti-C difficile toxin Abinding and neutralising activity was retained. Passive oral immunotherapy with anti-C difficile BIC maybe a useful non-antibiotic approach to the prevention and treatment ofC difficile antibiotic associated diarrhoeaand colitis.

Keywords:pseudomembranous colitis; toxin; diarrhoea; IgG; immunotherapy; antibiotic; Clostridiumdifficile

     

Physiological and performance adaptations of elite Greco-Roman wrestlers during a one-day tournament

The aim of this study was to determine the effects of a simulated one-day Greco-Roman wrestling tournament on selected performance and inflammatory status indices. Twelve competitive wrestlers (22.1 ± 1.3 years) completed five matches according to the official Olympic wrestling tournament regulations following a ~6% weight loss. Performance measurements, muscle damage assessment, and blood sampling were performed before and following each match. Performance and inflammatory markers were not affected by weight loss. Mean wrestling heart rate reached ~85% of maximal and lactate concentration exceeded 17 mM. Fatigue rating demonstrated a progressive rise (P < 0.05) throughout the tournament, peaking in match 4. Performance demonstrated a progressive deterioration (P < 0.05) throughout the tournament, especially in the last two matches (P < 0.05), with upper-body measures exhibiting a greater decline (P < 0.05) and remaining below baseline (P < 0.05) until the end of the tournament. Muscle damage markers increased during the course of the tournament with upper limbs affected more. Creatine kinase activity, CRP levels, IL-6 concentration, and leukocyte counts increased (P < 0.05) progressively throughout the tournament, peaking in the last two matches. Cortisol, epinephrine and norepinephrine increased (P < 0.05) after each match, but testosterone declined (P < 0.05) progressively, reaching a nadir before the last match. This inflammatory response was accompanied by a marked increase (p < 0.05) in lipid peroxidation, protein oxidation, and antioxidant status markers indicating the development of oxidative stress. These results suggest that a one-day wrestling tournament may induce significant physiological demands on wrestlers that may adversely affect their performance and inflammatory status especially during the later stages of the tournament.     

Role of substance P in the regulation of glucose metabolism via insulin signaling-associated pathways

Substance P (SP), encoded by the tachykinin 1 (Tac1) gene, is the most potent tachykinin ligand for the high-affinity neurokinin-1 receptor (NK-1R). We previously reported that NK-1R-deficient mice show less weight gain and reduced circulating levels of leptin and insulin in response to a high-fat diet (HFD) and demonstrated the presence of functional NK-1R in isolated human preadipocytes. Here we assessed the effects of SP on weight gain in response to HFD and determined glucose metabolism in Tac1-deficient (Tac1(-/-)) mice. The effect of SP on the expression of molecules that may predispose to reduced glucose uptake was also determined in isolated human mesenteric, omental, and sc preadipocytes. We show that although weight accumulation in response to HFD was similar between Tac1(-/-) mice and wild-type littermates, Tac1(-/-) mice demonstrated lower glucose and leptin and increased adiponectin blood levels and showed improved responses to insulin challenge after HFD. SP stimulated phosphorylation of c-Jun N-terminal kinase, protein kinase C, mammalian target of rapamycin, and inhibitory serine insulin receptor substrate-1 phosphorylation in human preadipocytes in vitro. Preincubation of human mesenteric preadipocytes with the protein kinase C pseudosubstrate inhibitor reduced insulin receptor substrate 1 phosphorylation in response to SP. Lastly, SP also induced insulin receptor substrate-1 phosphorylation in mature human sc adipocytes. Our results demonstrate an important role for SP in adipose tissue responses and obesity-associated pathologies. These novel SP effects on molecules that enhance insulin resistance at the adipocyte level may reflect an important role for this peptide in the pathophysiology of type 2 diabetes.     

Primary malignant melanoma of the oral mucosa.

PURPOSE: The occurrence of primary oral melanoma is very rare. Large clinical series suggesting appropriate treatment modalities are lacking; the clinician has to rely on case reports to gain insight into the management of this tumor, which is much more aggressive than its skin counterpart.Patients and methods The cases of 5 patients with primary oral melanoma during a 6-year period were retrospectively reviewed. Four patients presented with tumors located in the maxilla. Preoperative workup included microscopic examination of incisional biopsy specimens for the confirmation of the diagnosis and thorough imaging of the body to rule out distant metastases. Histologically significant vertical invasion was found in all patients. No patient had distant metastases initially, and only 1 patient presented with neck disease. Primary treatment included wide local excision in 4 patients and therapeutic modified radical neck dissection in the 1 patient with neck node involvement on presentation. One patient was treated primarily with radiation therapy due to medically compromised status. Adjuvant immunochemotherapy (DAV protocol) was administered to 4 patients. Radiation therapy was used in an adjuvant fashion in 3 patients. RESULTS: All of the patients developed distant metastases to the lung and liver and eventually died of their disease. Survival ranged from 14 to 38 months (mean, 25.6 months). Local recurrence occurred in 1 patient and was attributed to positive surgical margins. Contralateral neck disease developed in the patient who underwent therapeutic neck dissection. CONCLUSIONS: The prognosis of primary oral melanoma remains poor despite adequate locoregional control of the disease. It seems that diagnosis is made late in the course of the disease when the primary tumor has already shed microscopic distant metastases.