Occupational risk of blood-borne viruses in healthcare workers: a 5-year surveillance program.

OBJECTIVE: This study presents the results of a 5-year surveillance program involving the prospective follow-up of healthcare workers (HCWs) in the Veneto region of Italy exposed to blood-borne viruses. DESIGN: All HCWs who reported an occupational exposure to blood-borne infection joined the surveillance program. Both HCWs and patients were tested for viral markers (hepatitis B surface antigen [HBsAg], antibody to hepatitis B surface antigen [anti-HBs], antibody to hepatitis B core antigen [anti-HBc], antibody to hepatitis C virus [anti-HCV], HCV RNA, and antibody to human immunodeficiency virus [HIV]) and had these markers plus transaminases assayed at 3, 6, and 12 months and then yearly thereafter. Moreover, a program of hepatitis B virus (HBV) prophylaxis was offered to those whose anti-HBs levels were less than 10 IU/mL. PARTICIPANTS: Two hundred forty-five HCWs (156 women and 89 men) with a mean age of 37 (+/- 10) years who reported occupational exposure during the 5-year period. RESULTS: At the time of exposure, 1 HCW was positive for HBsAg (0.4%) and 2 were positive for HCV RNA (0.8%). Among the patients involved, 28 (11.4%) were positive for HBsAg, 68 (27.8%) were positive for HCV RNA, 6 (2.4%) were positive for HIV, and 147 (60.0%) were negative for all viral markers (4 patients were positive for both HCV and HIV). During the follow-up period after exposure (mean, 2.7 [+/- 1.6] years), there was no increase in transaminases or seroconversions to any of the viral markers. CONCLUSION: Our accurate postexposure follow-up revealed a lack of transmission of HBV, HCV, and HIV.     

Glucose transporter/T1R3-expressing cells in rat tracheal epithelium

Glucose transport plays an important role in maintaining low sugar concentration in airway surface liquid (ASL), which is critical for mucociliary clearance and bacterial colonization. Experimental evidence indicates that glucose/hexose uptake in lung/airway cells occurs by means of two structurally distinct glucose transporter pathways: the Na(+) -dependent glucose transporters (SGLT family) and the facilitative glucose transporters (GLUT family). In this study, we examined the expression of the major glucose transporters of the intestine, GLUT2, GLUT5, SGLT1 and T1R3 taste receptor subunit, in the trachea of rats using immunohistochemistry and immunoelectron microscopy, and compared them using double-labeled confocal microscopy. We found that GLUT2, GLUT5, SGLT1 and T1R3 are selectively expressed in different cell types. T1R3 and GLUT2 are predominantly expressed in subsets of solitary chemoreceptor cells (SCCs) and ciliated cells, GLUT5 is present in subsets of SCCs and in secretory cells, and SGLT1 is exclusively expressed in a unique cell type, SCCs. Furthermore, we demonstrated that T1R3 is colocalized with SGLT1 in SCCs and with GLUT2 transporter in ciliated cells. In conclusion, these findings reveal that different cell types are associated with the uptake of glucose in ASL and that, due to their T1R3 expression, SCCs and ciliated cells are most likely to participate in the chemosensory process in ASL.     

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Carbamazepine

Literature relevant to assessing whether BCS-based biowaivers can be applied to immediate release (IR) solid oral dosage forms containing carbamazepine as the single active pharmaceutical ingredient are reviewed. Carbamazepine, which is used for the prophylactic therapy of epilepsy, is a non-ionizable drug that cannot be considered “highly soluble” across the range of pH values usually encountered in the upper gastrointestinal tract. Furthermore, evidence in the open literature suggests that carbamazepine is a BCS Class 2 drug. Nevertheless, the oral absolute bioavailability of carbamazepine lies between 70 and 78% and both in vivo and in vitro data support the classification of carbamazepine as a highly permeable drug. Since the therapeutic and toxic plasma level ranges overlap, carbamazepine is considered to have a narrow therapeutic index. For these reasons, a BCS based biowaiver for IR tablets of carbamazepine cannot be recommended. Interestingly, in nine out of ten studies, USP dissolution conditions (900 mL water with 1% SLS, paddle, 75 rpm) appropriately discriminated among bioinequivalent products and this may be a way forward to predicting whether a given formulation will be bioequivalent to the comparator product.     

Dissolution Methods to Increasing Discriminatory Power of In Vitro Dissolution Testing for Ibuprofen Free Acid and Its Salts

The predictive capacity of in vitro dissolution tests using the Biopharmaceutics Classification System (BCS)–based experimental setup to anticipate in vivo bioequivalence outcomes for BCS class 2 weak acids has been questioned. In this work, the effect of buffer concentration media was investigated as a possible approach to ensuring the discriminative capacity of the in vitro dissolution methods. The case example used to test this approach was ibuprofen, formulated as either the free acid or in various salt forms. By matching the concentration of buffers commonly used to prepare media which aim to simulate the intestinal conditions with that of bicarbonate buffer, which is the predominant buffer species in vivo, to arrive at the same surface pH (pH₀), the discriminative power of the in vitro dissolution tests was improved. To simulate the in vivo results even better, a pretreatment at acidic pH was added to the dissolution test simulating the gastric conditions to create a 2-stage test. With the 2-stage test, it was possible to account for differences in disintegration in a more physiologically relevant way and thus to better reflect the in vivo performance of the various formulations.     

Immunohistochemical localization of Clara cell secretory proteins (CC10-CC26) and Annexin-1 protein in rat major salivary glands

The oral cavity is continuously bathed by saliva secreted by the major and minor salivary glands. Saliva is the first biological medium to confront external materials that are taken into the body as part of food or drink or inhaled volatile substances, and it contributes to the first line of oral defence. In humans, it has been shown that sputum and a variety of biological fluids contain Clara cell secretory proteins (CC10–CC26). Various studies of the respiratory apparatus have suggested their protective effect against inflammatory response and oxidative stress. Recently, CC10 deficiency has been related to the protein Annexin‐1 (ANXA1), which has immunomodulatory and anti‐inflammatory properties. Considering the defensive role of both Clara cell secretory proteins and ANXA1 in the respiratory apparatus, and the importance of salivary gland secretion in the first line of oral defence, we decided to evaluate the expression of CC10, CC26 and ANXA1 proteins in rat major salivary glands using immunohistochemistry. CC10 expression was found only in the ductal component of the sublingual gland. Parotid and submandibular glands consistently lacked CC10 immunoreactivity. In the parotid gland, both acinar and ductal cells were always CC26‐negative, whereas in the submandibular gland, immunostaining was localized in the ductal component and in the periodic acid Schiff (PAS)‐positive area. In the sublingual gland, ductal cells were always positive. Acinar cells were not immunostained at all. ANXA1 was expressed in ductal cells in all three major glands. In parotid and sublingual glands, acinar cells were negative. In submandibular glands, immunostaining was present in the mucous PAS‐positive portion, whereas serous acinar cells were consistently negative. The existence of some CC10‐CC26–ANXA1‐positive cells in rat salivary glandular tissue is an interesting preliminary finding which could support the hypothesis, suggested for airway tissue, that these proteins have a defensive and protective role. Protein expression heterogeneity in the different portions of the glands could be an important clue in further investigations of their role.