Determination of iodide in metabolic studies of 125I-labeled compounds.

Methods capable of measuring inorganic iodide in the presence of other highly polar metabolites were developed in support of studies concerning the metabolism of 125I-labeled compounds. The methods included separation of iodine on a weakly basic resin paper followed by gamma-counting, methyl iodide exchange, and reverse isotopic dilution.     

Vestibular afferent innervation in the vestibular efferent nucleus of rats

To delineate the vestibular afferent innervation in the vestibular efferent nucleus in the brainstem, neurobiotin or biotinylated dextran amine was injected into the superior Scarpa's ganglion of Sprague-Dawley rats. The locations of vestibular efferent neurons in the brainstem were identified by neutral red or choline acetyltransferase staining. Of the three pairs of vestibular efferent nuclei, labeled fibers and bouton-like endings were found only within the dorsolateral vestibular efferent nucleus on the ipsilateral side. Labeled afferent terminals with bouton-like varicosities were observed in the vicinity of cell bodies or dendrites of these efferent neurons. Our findings suggest that vestibular primary afferents may exert direct influence on vestibular efferent neurons, constituting an ipsilateral close-loop arrangement in the central vestibular system.     

OPERATIVE CHOLANGIOGRAPHY: EVALUATION OF ITS ROUTINE USE IN 569 CHOLECYSTECTOMIES1

From 1974 till 1979, 569 cholecystectomies with routine operative cholangiography were performed in the university surgical unit, Kwong Wah Hospital, Hong Kong, for non-malignant diseases of the gallbladder. Gallstones were present in 522 cases. Acalculous cholecystitis occurred in 47 cases. At least one of the clinical or operative indications to explore the common bile duct was present in 312 of the patients. However, in this group of patients in whom routine operative cholangiography was done, exploration of the common bile duct was performed in only 147, thus avoiding unnecessary exploration of the duct in 165 cases (52.8%). In the remaining 257 patients in whom there was no indication to explore the common bile duct, operative cholangiography revealed unexpected stones in the common bile duct in 14 (5.5%). After choledochotomy, post exploratory operative T-tube cholangiography was performed to rule out overlooked stones, which were present in six cases (6/161, i.e., 3.7%). Postoperative T-tube cholangiography performed on the 12th to the 14th postoperative day showed retained stones in 17 cases, giving an incidence of known retained stones of 11% (17/161) of cholecystectomies with exploration of the common bile ducts, or 3% (17/569) in the whole series of     

Bupreorphine:a new pharmacotherapy for opioid addictions treatment

The federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with the disease of addiction by providing increased access to options for treatment. Previously, only methadone maintenance, approved for use only through specially regulated clinics, was available to treat opioid addiction. DATA allows any physician choosing to take a short specialty training course and become certified to prescribe buprenorphine. Buprenorphine and buprenorphine/ naloxone (Subutex, Suboxone) can be prescribed by certified physicians in a traditional office setting to treat patients with opioid dependence. Clinical studies indicate buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and reducing illicit opioid use. Sublingual buprenorphine is more effective than clonidine or clonidine/naltrexone in short-term opioid detoxification treatment. Buprenorphine provides an additional tool to treat opioid addiction and improve the quality of lives of these patients. More physicians are needed to treat patients with addiction. DATA facilitates this by removing existing barriers and increasing access to treatment.     

Regulation of Osteoclasts by Calcitonin and Amphiphilic Calcitonin Conjugates: Role of Cytosolic Calcium

The peptide hormone calcitonin is a potent inhibitor of osteoclastic resorption, but it is unstable and poorly absorbed following oral administration. Conjugates of salmon calcitonin covalently linked to low-molecular-weight amphiphilic polymers show improved stability and absorption. The purpose of this study was to investigate the biological activity of these conjugates in vitro using rat osteoclasts and HEK-293 cells transfected with the C1a isoform of the calcitonin receptor. Salmon calcitonin or its conjugates (10 pM–10 nM) caused rapid arrest of osteoclast membrane ruffling and subsequent retraction. The same amphiphilic polymer attached to an unrelated protein had no effect on osteoclast morphology or motility. Since calcitonin-induced retraction of osteoclasts is thought to be mediated by Ca²⁺ signaling, we investigated the effects of calcitonin and its conjugates on cytosolic free Ca²⁺ concentration ([Ca²⁺]_i). In HEK-293 cells transfected with the calcitonin receptor, these agents induced transient elevations of [Ca²⁺]_i. However, the rise of [Ca²⁺]_i in HEK-293 cells occurred at concentrations 100–1000-fold higher than those required to elicit osteoclast retraction. To investigate the role of Ca²⁺ in osteoclast retraction, we preloaded cells with BAPTA to buffer changes in [Ca²⁺]_i. BAPTA decreased the initial rate of calcitonin-induced osteoclast retraction, but it did not affect the degree of retraction 2–3 hours following calcitonin, indicating that retraction is mediated primarily by Ca²⁺-independent processes. We conclude that calcitonin conjugates cause osteoclast retraction and [Ca²⁺]_i signaling in a manner similar to that elicited by calcitonin. Thus, orally bioavailable calcitonin conjugates show potential for use as antiresorptive agents.     

Treatment with a short course of LF 15-0195 and continuous cyclosporin A attenuates acute xenograft rejection in a rat-to-mouse cardiac transplantation model

Searching for a novel immunosuppressive agent to effectively prevent acute vascular rejection (AVR) is essential for success in clinical xenotransplantation. We previously reported that Lewis rat hearts transplanted into BALB/c mice developed typical AVR in 6 days. The present study was undertaken to determine the efficacy of LF 15-0195, a new immunosuppressive analog of 15-deoxyspergualin in the prevention of AVR in a rat-to-mouse cardiac xenograft model. We transplanted 2-week old Lewis rat hearts into BALB/c mice. Four groups were included in this study: untreated recipients and cyclosporin A (CsA) treated recipients were controls; LF 15-0195 treated recipients or LF 15-0195 combined with CsA treated recipients were experimental groups. Mouse recipients received either LF 15-0195 2 mg/kg subcutaneously from day-1 to post-operative day 14, or CsA 15 mg/kg subcutaneously daily, from day 0 to endpoint rejection, or the two drugs in combination. We observed that high dose CsA did not inhibit AVR and the graft was rejected in 11.3 +/- 1.9 days. Graft histology and immunohistology showed typical AVR, characterized by interstitial hemorrhage, intravascular fibrin deposition, thrombosis, and massive deposition of anti-rat immunoglobulin G (IgG) and immunoglobulin M (IgM). Serum xenoreactive antibodies (xAbs) were markedly elevated in these animals as well. In contrast, we observed that treatment with LF 15-0195 alone significantly prolonged graft survival to 19.3 +/- 0.7 days. Notably, xAbs were significantly decreased and the rejection pattern of these grafts was cell-mediated rejection (CMR), instead of AVR. When CsA was combined with LF 15-0195, the graft mean survival time was further increased to 58.5 +/- 17.3 days. Antibody production and T-cell infiltration were significantly inhibited at the terminal stages of graft survival and pathology showed striking attenuation of both AVR and CMR. Sequential studies on days 6 and 14 demonstrated that LF 15-0195 either alone or combined with CsA completely inhibited antibody production. However, intragraft infiltration by Mac-1 positive cells including natural killer cells, macrophages and granulocytes in LF 15-0195 treated recipients was similar to that of untreated recipients. We conclude that LF 15-0195 effectively prevented AVR by markedly inhibiting the production of anti-donor IgG xAbs. Also, treatment with short course LF 15-0195 and continuous CsA significantly reduced T-cell infiltration. Studies to test this therapy in inhibiting AVR in a pig-to-non-human primate xenotransplantation model are underway.     

Occupational contact dermatitis to nickel: experience of the British dermatologists (EPIDERM) and occupational physicians (OPRA) surveillance schemes

Aims: To examine, from occupational surveillance reporting data, whether scheme reporters considered nickel exposure to play a role in occupational contact dermatitis (OCD) in the UK.

Methods: Data on occupational skin disease in the UK are collected by two occupational disease surveillance schemes, EPIDERM and OPRA. Cases of OCD believed to have relevant nickel exposure reported to EPIDERM or OPRA from February 1993 to January 1999 were studied.

Results: An estimate of 1190 cases of occupational contact dermatitis thought to have relevant nickel exposure (12% of total estimated OCD) was derived from reports by dermatologists, an average of 198 per year. The highest incidence rates were seen in hairdressers (23.9/100 000 workers/year), bar staff (4.7), chefs and cooks (4.4), retail cash and checkout operators (2.8), and catering assistants (2.5). From May 1994 to January 1999, 158 cases of nickel associated dermatitis (1.9% of total OCD cases) were estimated; the most frequently reported occupations were electronic assemblers, nurses, sales assistants, and general assemblers. From July 1997 to January 1999, 547 positive patch tests to nickel were reported; in 195 cases (36%), nickel was felt to be a relevant occupational allergen (for example, coin handling). In hairdressers, nurses, cooks, and beauticians, nickel was usually considered, if relevant at all, to be only one of several causes of dermatitis.

Conclusions: Up to 12% of total estimated cases of OCD were thought to be due in part to nickel. Results suggest that nickel hypersensitivity is one of several contributors to OCD in subjects with multiple occupational exposures. Coin handling may be a source of OCD to nickel.