Is there a healthy migrant effect in relation to oral health among adults in England?

OBJECTIVE: The aim of the study was to assess the healthy migrant effect in relation to oral health among adults in England. STUDY DESIGN: This is a secondary data analysis of a nationally representative survey. METHODS: Data from 13,373 adults of Irish, black Caribbean, Indian, Pakistani, Bangladeshi and Chinese ethnicity, who participated in the Health Survey for England, were analysed. The proportions of edentate and dentate adults with toothache in the last 6 months in first- and second-generation migrants within each ethnic group were compared with those in the white British (reference group) ethnic group in logistic regression models after adjusting for demographic factors and socio-economic position. Among first-generation migrants, the associations of age at arrival and length of residence with each oral health outcome were assessed in logistic regression models after adjusting for sociodemographic factors. RESULTS: Compared with white British migrants, first-generation black Caribbean (odds ratio [OR]: 1.42) and second-generation Pakistani (OR: 3.16) migrants had higher odds of being edentulous, whereas first-generation Indian (OR: 0.62), Pakistani (OR: 0.62), Bangladeshi (OR: 0.41) and Chinese (OR: 0.49) migrants had lower odds. Among dentate adults, second-generation Irish (OR: 1.51) migrants, first- and second-generation black Caribbean (OR: 1.61 and 1.54, respectively) migrants, first-generation Indian (OR: 1.24) migrants and second-generation Pakistani (OR: 1.34) migrants had higher odds of having toothache in the past 6 months, whereas second-generation Bangladeshi (OR: 0.51) migrants had lower odds than white British. Age at arrival and length of residence were positively associated with being edentulous among first-generation black Caribbean, Pakistani and Bangladeshi migrants. CONCLUSION: Evidence on the healthy migrant effect was mixed, with more consistent findings seen for edentulousness among Asian groups. Black Caribbean migrants were generally the ethnic group with the worst oral health when compared with white British.

Dealing with the high cost of biological therapies: developing and implementing a biological therapy prioritization protocol for ankylosing spondylitis patients in a tertiary hospital.

OBJECTIVE: In January 2011, a biological therapies commission was created in our hospital to fully address the management of biological drugs. A biological therapy prioritization protocol was developed for ankylosing spondylitis (AS) patients. Here, we describe it and report on its economic impact to illustrate how we are optimizing the use of these expensive new drugs. METHODS: The biological therapies commission established several procedures for the rational use of biological drugs such as cost-efficiency therapeutic protocols, pharmacovigilance, and therapeutic drug monitoring programs. The AS protocol was based on clinical and economic aspects. We estimated the economic impact of the protocol by comparing the cost of treating AS patients with biological drugs in the pre-commission (2009 - 2010) vs. post-commission period (2011 - 2013). AS patients treated with adalimumab (ADA), etanercept (ETN) or infliximab (IFX) for at least 6 months in the 2009 - 2013 period were included. RESULTS: 107 patients were included. In the pre-commission period, total expenses increased by +30,944 Euro (+4%). After protocol implementation, total expenses decreased by 11,441 Euro (-1%) during 2011, and by an additional 36,781 Euro (-4%) and 53,872 Euro (-8%) in 2012 and 2013, respectively. In the 2010 - 2013 period the cost of biological therapy per patient-year decreased by 869 €, suggesting the positive effects of the biological therapy prioritization protocol instauration. CONCLUSION: We describe the establishment of a multidisciplinary biological therapy commission to optimize the use of biological therapies. We illustrate its work in developing a protocol for the management of AS patients with such therapies. We show that after 3-years of implementation, the biological therapy prioritization protocol allowed us to steadily decrease the direct cost of biological drug therapies per patient, up to 869 Euro.

Effectiveness of infliximab, adalimumab and golimumab for non-infectious refractory uveitis in adults.

AIM: To discuss the available data regarding the off-label uses of anti-TNF agents in non-infectious uveitis. DATA SOURCE: A literature search was performed in Medline through PubMed from January 2001 to January 2014. STUDY SELECTION AND DATA EXTRACTION: English-language articles about uveitis treatment with anti-TNF drugs in adult patients were reviewed. DATA SYNTHESIS: The use of anti-TNF-Î ± drugs for treatment of several refractory manifestations of refractory uveitis in adult patients is increasing. However, due to the lack of evidence from randomized controlled trials, the use of anti-TNF in uveitis remains “off-label” in most countries. There is no trial-based evidence to support it except for the experience provided by cases and case series. This experience, which is continuously increasing, has yielded encouraging results. Anti-TNF-Î ± drugs, such as infliximab, adalimumab, and golimumab, are reasonably effective for controlling ocular inflammation and sparing patients corticosteroid treatment in non-infectious refractory uveitis. Approximately 80% of patients on infliximab, adalimumab, or golimumab were able to achieve sustained control of inflammation by 6 months. CONCLUSION: Anti-TNF-Î ± therapy is effective in inducing clinical remission for refractory uveitis, with a relatively low rate of treatment-ending adverse events. However, randomized and controlled trials are required to adequately assess the maintained clinical efficacy and safety profile in the long term of anti-TNF agents for non-infectious refractory uveitis.

[Predictors of the use of the early invasive strategy in women with non-ST-elevation acute coronary syndrome]. / Predictores del uso de la estrategia invasiva precoz en mujeres con síndrome coronario agudo sin elevación de ST.

OBJECTIVE: To identify determinants associated to an early invasive strategy in women with acute coronary syndromes without ST elevation (NSTE-ACS). DESIGN: A retrospective cohort study was made. Crude and adjusted analysis of the performance of the early invasive strategy using logistic regression. SETTING: Coronary Units enrolled in 2010 - 2011 in the ARIAM-SEMICYUC registry. PATIENTS: A total of 440 women with NSTE-ACS were studied. Sixteen patients were excluded due to insufficient data, together with 58 patients subjected to elective coronary angiography (> 72 h). VARIABLES ANALYZED: Demographic parameters, coronary risk factors, previous medication, comorbidity. Clinical, laboratory, hemodynamic and electrocardiographic data of the episode. RESULTS: Women treated conservatively were of older age, had oral anticoagulation, diabetes, previous coronary lesions, and heart failure (p<0.005), increased baseline bleeding and ischemic risk (p=0.05) and a higher heart rate upon admission (p<0.05). After adjustment, only age > 80 years (OR 0.48, 95% CI 0.27 to 0.82, p=0.009), known coronary lesions (OR 0.47, 95% CI 0.26-0.84, p=0.011), and heart rate (OR 0.98, 95% CI 0.97-0.99, p=0.003) were independently associated to conservative treatment. Smoking (OR 2.50, 95% CI 1.20 to 5.19, p=0.013) and high-risk electrocardiogram (OR 2.96, 95% CI 1.72 to 4.97, p<0.001) were associated to the early invasive strategy. The exclusion of early deaths (<24 h) did not alter these results. CONCLUSIONS: In women with NSTE ACS, smoking and a high-risk electrocardiogram upon admission were independent factors associated to the early invasive strategy. Previous coronary lesions, age > 80 years and increased heart rate were independent factors associated to conservative treatment.

Pathobiology and transmission of highly and low pathogenic avian influenza viruses in European quail (Coturnix c. coturnix).

European quail (Coturnix c. coturnix) may share with Japanese quail (Coturnix c. japonica) its potential as an intermediate host and reservoir of avian influenza viruses (AIV). To elucidate this question, European quail were experimentally challenged with two highly pathogenic AIV (HPAIV) (H7N1/HP and H5N1/HP) and one low pathogenic AIV (LPAIV) (H7N2/LP). Contact animals were also used to assess the viral transmission among birds. Severe neurological signs and mortality rates of 67% (H7N1/HP) and 92% (H5N1/HP) were observed. Although histopathological findings were present in both HPAIV-infected groups, H5N1/HP-quail displayed a broader viral antigen distribution and extent of microscopic lesions. Neither clinical nor pathological involvement was observed in LPAIV-infected quail. Consistent long-term viral shedding and effective transmission to naive quail was demonstrated for the three studied AIV. Drinking water arose as a possible transmission route and feathers as a potential origin of HPAIV dissemination. The present study demonstrates that European quail may play a major role in AI epidemiology, highlighting the need to further understand its putative role as an intermediate host for avian/mammalian reassortant viruses.

[Early invasive strategy in non-ST-segment elevation acute coronary syndrome. The paradox continues]. / Uso de la estrategia invasiva precoz en el síndrome coronario agudo sin elevación de ST. La paradoja continúa.

OBJECTIVE: Observational studies have reported a paradoxical inverse relationship between the use of an early invasive strategy (EIS) and the risk of events in patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS). The study objectives are: 1) to examine the association between baseline risk in patients with NSTE ACS and the use of EIS; and 2) to identify some of the factors independently associated to the use of EIS. DESIGN: Retrospective cohort study. SETTING: Intensive care units participating in the SEMICYUC ARIAM Registry. PATIENTS: Consecutive patients admitted with a diagnosis of NSTE-ACS within 48 hours of evolution between the months of April-July 2010. INTERVENTIONS: None. MAIN OUTCOMES: Coronary angiography with or without angioplasty within 72 hours, risk stratification using the GRACE scale. RESULTS: We analyzed 543 patients with NSTE-ACS, of which 194 were of low risk, 170 intermediate risk and 179 high risk. The EIS was used in 62.4% of the patients at low risk, in 60.2% of those with intermediate risk, and in 49.7% of those at high risk (p for tendency 0.0144). The EIS was used preferentially in patients with low severity and comorbidity. In the logistic regression model, EIS was independently associated to the availability of a catheterization laboratory (OR 2.22 [CI 95% 1.55 to 3.19]), the presence of ST changes on ECG (OR 1.80 [1.23 to 2.64]), or the existence of a low risk of bleeding (OR 0.76 [0.66 to 0.88)]. Conversely, EIS was less prevalent in patients with diabetes (OR 0.60 [0.41 to 0.88]) or tachycardia upon admission (OR 0.54 [0 36 to 0.82]). CONCLUSIONS: In 2010 there remained a lesser relative use of EIS in patients at high risk, due in part to an increased risk of bleeding in these patients.

Pathogenesis of highly pathogenic avian influenza A virus (H7N1) infection in chickens inoculated with three different doses.

To study the pathogenesis of a H7N1 highly pathogenic avian influenza virus strain, specific pathogen free chickens were inoculated with decreasing concentrations of virus: 10(5.5) median embryo lethal dose (ELD(50)) (G1), 10(3.5) ELD(50) (G2) and 10(1.5) ELD(50) (G3). Disease progression was monitored over a period of 16 days and sequential necropsies and tissue samples were collected for histological and immunohistochemical examination. Viral RNA loads were also quantified in different tissues, blood, oropharyngeal swabs, and cloacal swabs using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Clinical signs of depression, apathy, listlessness, huddling and ruffled feathers were recorded in G1 and a few G2 birds, whilst neurological signs were only observed in chickens inoculated with the highest dose. Gross lesions of haemorrhages were observed in the unfeathered skin of the comb and legs, and skeletal muscle, lung, pancreas and kidneys of birds inoculated with 10(5.5) ELD(50) and 10(3.5) ELD(50) doses. Microscopic lesions and viral antigen were demonstrated in cells of the nasal cavity, lung, heart, skeletal muscle, brain, spinal cord, gastrointestinal tract, pancreas, liver, bone marrow, thymus, bursa of Fabricius, spleen, kidney, adrenal gland and skin. Viral RNA was detected by RT-qPCR in kidney, lung, intestine, and brain samples of G1 and G2 birds. However, in birds infected with the lowest dose, viral RNA was detected only in brain and lung samples in low amounts at 5 and 7 days post infection. Interestingly, viral shedding was observed in oropharyngeal and cloacal swabs with proportionate decrease with the inoculation dose. We conclude that although an adequate infectious dose is critical in reproducing the clinical infection, chickens exposed to lower doses can be infected and shed virus representing a risk for the dissemination of the viral agent.

Cross-Cultural Measurement Invariance in the Personality Inventory for DSM-5✰.

The validity of cross-cultural comparisons of test scores requires that scores have the same meaning across cultures, which is usually tested by checking the invariance of the measurement model across groups. In the last decade, a large number of studies were conducted to verify the equivalence across cultures of the dimensional Alternative Model of Personality Disorders (DSM-5 Section III). These studies have provided information on configural invariance (i.e., the facets that compose the domains are the same) and metric invariance (i.e., facet-domain relationships are equal across groups), but not on the stricter scalar invariance (i.e., the baseline levels of the facets are the same), which is a prerequisite for meaningfully comparing group means. The present study aims to address this gap. The Personality Inventory for DSM-5 (PID-5) was administered to five samples differing on country and language (Belgium, Catalonia, France, Spain, and Switzerland), with a total of 4,380 participants. Configural and metric invariance were supported, denoting that the model structure was stable across samples. Partial scalar invariance was supported, being minimal the influence of non-invariant facets. This allowed cross-cultural mean comparisons. Results are discussed in light of the sample composition and a possible impact of culture on development of psychopathology.

Persistence of highly pathogenic avian influenza virus (H7N1) in infected chickens: feather as a suitable sample for diagnosis.

Selection of an ideal sample is a vital element in early detection of influenza infection. Rapid identification of infectious individuals or animals is crucial not only for avian influenza virus (AIV) surveillance programmes, but also for treatment and containment strategies. This study used a combination of quantitative real-time RT-PCR with an internal positive control and a cell-titration system to examine the presence of virus in different samples during active experimental AIV infection and its persistence in the infected carcasses. Oropharyngeal/cloacal swabs as well as feather pulp and blood samples were collected from 15-day-old chicks infected with H7N1 highly pathogenic AIV (HPAIV) and the kinetics of virus shedding during active infection were evaluated. Additionally, several samples (muscle, skin, brain, feather pulp and oropharyngeal and cloacal swabs) were examined to assess the persistence of virus in the HPAIV-infected carcasses. Based on the results, feather pulp was found to be the best sample to detect and isolate HPAIV from infected chicks from 24 h after inoculation onwards. Kinetic studies on the persistence of virus in infected carcasses revealed that tissues such as muscle could potentially transmit infectious virus for 3 days post-mortem (p.m.), whilst other tissues such as skin, feather pulp and brain retained their infectivity for as long as 5-6 days p.m. at environmental temperature (22-23 degrees C). These results strongly favour feather as a useful sample for HPAIV diagnosis in infected chickens as well as in carcasses.

Urticaria due to etanercept in a patient with psoriatic arthritis.

A 50-year-old woman was referred to our emergency room because of urticaria. Eleven days after etanercept therapy was started, the patient developed an urticarial rash of the trunk and face. A diagnosis of generalized urticaria was made. Etanercept treatment was suspended. Treatment was started with methylprednisolone and dexchlorpheniramine. The patient's condition improved and she was discharged. In this case, the most probable cause of urticaria was considered to be etanercept because of the temporal relationship between exposure to the drug and the onset of symptoms. The adverse reaction could be considered probable. Although the overall risk of skin adverse events associated with etanercept appears low, clinicians should be aware of this reaction.

Septic shock and community-acquired pneumonia associated with etanercept therapy.

OBJECTIVE: To report a case of septic shock and community-acquired pneumonia in a patient with psoriatic arthritis receiving treatment with etanercept. PATIENT DETAILS: A 65-year-old woman diagnosed as having psoriatic arthritis had received treatment with etanercept. Chest X-ray studies were normal and the tuberculin skin test was negative. Two months after etanercept therapy, the patient presented to our emergency department with fever, cough, chest pain and generalized weakness. Chest radiography revealed a right pulmonary infiltrate. Her condition rapidly deteriorated and she went into shock with a further drop in her blood pressure, tachycardia and tachypnea. She was intubated, mechanically ventilated and was treated with fluids, cardioversion and amiodarone. Empiric therapy with levofloxacin, amikacin and cefepime were initiated. In the urinalysis, the result of a rapid test for Streptococcus pneumoniae was positive. Etanercept treatment was suspended due to a possible adverse reaction associated with this drug. At the start of therapy her clinical condition improved slowly. On Day 28, the patient was afebrile and she was discharged from the intensive care unit. DISCUSSION: Most of the infections associated with etanercept therapy have been reported in patients with rheumatoid arthritis. Based on our observations, etanercept was the possible offender in the development of septic shock and respiratory failure in community-acquired pneumonia. There was a temporal relationship between exposure to the drug and onset of symptoms. Etanercept was the only drug administered before the septic shock developed. Based on the Naranjo algorithm, the adverse reaction could be considered possible. CONCLUSION: Patients initiated on etanercept should be counseled and receive appropriate screening before drug initiation. All febrile and newly occurring concomitant illnesses should be promptly evaluated. General practitioners should discontinue etanercept treatment and institute prompt and aggressive intervention if infection develops.

Severe stomatitis complicating treatment with pegylated-interferon alpha-2a and ribavirin in an HCV-infected patient.

OBJECTIVE: To report a case of severe stomatitis probably induced by peginterferon alpha-2a. METHODS AND RESULTS: A 42-year-old man with chronic hepatitis C genotype 1b commenced treatment with peginterferon alpha-2a 180 microg subcutaneously weekly and ribavirin 1000 mg/d orally. Twenty-eight days after commencing treatment, the patient experienced difficulties with swallowing, dryness of the mouth, stomatitis, and pain. Diagnosis of stomatitis was made. He did not complain of any other adverse effect of peginterferon alpha-2a and ribavirin. Both medications were discontinued. The withdrawal of peginterferon alpha-2a was followed by the resolution of the oral lesions in three weeks. The patient was followed up in the outpatient clinic at one month and at three months, and he was asymptomatic. CONCLUSIONS: Manufacturers of peginterferon alpha-2a suggest that mouth ulceration, stomatitis, dysphagia, and glossitis are considered adverse reactions of this medication. In this case, the most likely cause of the stomatitis was considered to be peginterferon alpha-2a because of the close temporal relationship between exposure to the drug and onset of symptoms, as well as the rapid resolution of the symptoms and signs after peginterferon alpha-2a was discontinued. An objective causality assessment revealed that a adverse drug event was possible. Clinicians should be aware of this potentially adverse effect of a widely used drug.

Parapharyngeal abscess in a patient receiving etanercept.

OBJECTIVE: To report a case of parapharyngeal abscess associated with Streptococcus viridans in a patient with rheumatoid arthritis receiving treatment with etanercept. CASE SUMMARY: A 40-year-old man diagnosed with rheumatoid arthritis had received treatment with nonsteroidal antiinflammatory drugs, methotrexate, and deflazacort. Six months prior to admission, the patient had a Disease Activity Score of 3.4; clinicians decided to start treatment with etanercept. Chest X-rays were normal and the tuberculin skin test was negative. Treatment with etanercept plus methotrexate was started. Three months later, methotrexate was discontinued. Six months after etanercept therapy was started, the patient presented to our emergency department with a swelling of his neck, odynophagia, otalgia, and trismus. The clinical course was consistent with parapharyngeal abscess. Etanercept treatment was suspended. The parapharyngeal abscess was drained and intravenous methylprednisolone, amoxicillin/clavulanic acid, and clindamycin were administered. The parapharyngeal abscess secretion culture was positive for S. viridans and Bacteroides spp. The patient's condition improved with antibiotic therapy; he was discharged 5 days after admission. DISCUSSION: Tumor necrosis factor-alpha plays an essential role in the immune-mediated response to infection. In our patient, the most possible cause of parapharyngeal abscess was considered to be etanercept because of the temporal relationship between exposure to the drug and onset of symptoms. Etanercept was the only drug administered before the abscess developed. Based on the Naranjo probability scale, an association between etanercept and the adverse reaction could be considered possible. CONCLUSIONS: Patients initiated on etanercept therapy should be closely monitored for the development of tuberculosis and other infections. During treatment, all febrile or novel illnesses should be evaluated promptly. If clinical evaluation leads to the suspicion of tuberculosis and other infections associated with etanercept, it should be discontinued immediately.

Middle East respiratory syndrome coronavirus experimental transmission using a pig model.

Dromedary camels are the main reservoir of Middle East respiratory syndrome coronavirus (MERS-CoV), but other livestock species (i.e., alpacas, llamas, and pigs) are also susceptible to infection with MERS-CoV. Animal-to-animal transmission in alpacas was reported, but evidence for transmission in other species has not been proved. This study explored pig-to-pig MERS-CoV transmission experimentally. Virus was present in nasal swabs of infected animals, and limited amounts of viral RNA, but no infectious virus were detected in the direct contact pigs. No virus was detected in the indirect contact group. Furthermore, direct and indirect contact pigs did not develop specific antibodies against MERS-CoV. Therefore, the role of pigs as reservoir is probably negligible, although it deserves further confirmation.

Advancing vector biology research: a community survey for future directions, research applications and infrastructure requirements.

Vector-borne pathogens impact public health, animal production, and animal welfare. Research on arthropod vectors such as mosquitoes, ticks, sandflies, and midges which transmit pathogens to humans and economically important animals is crucial for development of new control measures that target transmission by the vector. While insecticides are an important part of this arsenal, appearance of resistance mechanisms is increasingly common. Novel tools for genetic manipulation of vectors, use of Wolbachia endosymbiotic bacteria, and other biological control mechanisms to prevent pathogen transmission have led to promising new intervention strategies, adding to strong interest in vector biology and genetics as well as vector-pathogen interactions. Vector research is therefore at a crucial juncture, and strategic decisions on future research directions and research infrastructure investment should be informed by the research community. A survey initiated by the European Horizon 2020 INFRAVEC-2 consortium set out to canvass priorities in the vector biology research community and to determine key activities that are needed for researchers to efficiently study vectors, vector-pathogen interactions, as well as access the structures and services that allow such activities to be carried out. We summarize the most important findings of the survey which in particular reflect the priorities of researchers in European countries, and which will be of use to stakeholders that include researchers, government, and research organizations.

Disinfection of human enteric viruses on fomites.

The virucidal action of several commercially available disinfectant preparations was assayed against hepatitis A virus and human rotavirus dried on polystyrene. Overall, the level of virus disinfection achieved was very poor, usually inducing less than 3 log titre reduction. Suspension tests performed with the same disinfectants showed different virus inactivation rates, thus failing to provide a reliable indication of the actual virus disinfection on fomites. In our studies, bacteriophages of Bacteroides fragilis proved to be a simple, cheap and reliable screening tool for the evaluation of virus disinfection on non-porous surfaces. The same conclusion cannot be drawn for poliovirus.

The use of bacteriophages of Bacteroides fragilis as indicators of the efficiency of virucidal products.

The potential use of bacteriophage B40-8 of Bacteroides fragilis for the evaluation of the virucidal activity of antiseptics or disinfectants was investigated. The antiviral activity of two antiseptics and two disinfectants was evaluated according to a standard guideline. The effect of the virucidal agents was assessed on (i) viruses usually spread by direct contact with surfaces with contaminated secretions, i.e. herpes virus 1 and 2, and vaccinia virus, and (ii) viruses transmitted by the fecal-oral route, i.e. hepatitis A virus, poliovirus, adenovirus and rotavirus. The survival of B40-8 always equalled or exceeded that of the animal viruses tested. Our data suggest the use of bacteriophage B40-8 to complement the information furnished by some standardized methods in ascertaining the antiviral activity of virucidal preparations.

Concentration of fish enveloped viruses from large volumes of water.

The validity of several concentration procedures for the detection of fish enveloped viruses present in large volumes of water was determined. Viral haemorrhagic septicaemia virus (VHSV) was used to evaluate adsorption/elution to positively-charged MK filter cartridges for the concentration of enveloped viruses. For fresh water, the efficiency of the procedure ranged from 12 to 100%, with a mean recovery of 57%. In seawater samples, the recoveries varied from 15 to 100%, with a mean recovery of 59%. The same virus was used in methods such as organic flocculation and ammonium sulphate flocculation with very poor recoveries of infectious virus, caused by the inactivation of VHSV in both procedures. Concentration of seawater samples from tanks housing sea bass or gilthead affected by viral erythrocytic infection and lymphocystis, respectively, were carried out. In both cases, the viruses responsible for the outbreaks were detected by electron microscopy in the concentrated water samples.

Effects of omega-conotoxin MVIIC on veratridine-induced cytotoxicity and cytosolic Ca(2+) oscillations.

External Ca(2+) entry through various Ca(2+)-channel subtypes is responsible for the large oscillations of the cytosolic Ca(2+) concentrations, [Ca(2+)](i), and cell death induced by veratridine in primary cultures of bovine chromaffin cells. Blockade by omega-conotoxin GVIA (GVIA) of N-type Ca(2+) channels, by omega-agatoxin IVA (IVA) of P-type Ca(2+) channels, or by furnidipine of L-type Ca(2+) channels did not afford cytoprotection. However, (omega-conotoxin MVIIC (MVIIC), a wide-spectrum blocker of N-, P- and Q-type Ca(2+) channels greatly protected the cells against the cytotoxic effects of veratridine. Furnidipine further enhanced the cytoprotecting effects of MVIIC. MVIIC but not furuidipine, markedly reduced the oscillations of [Ca(2+)](i) induced by veratridine in single fura-2-loaded chromaffin cells. The results suggest that Ca(2+) entry through any of the different Ca(2+) channel subtypes present in bovine chromaffin cells might be cytotoxic. They also support two ideas: (i) that wide-spectrum neuronal Ca(2+) channel blockers (i.e. MVIIC) might be better cytoprotecting agents than more specific neuronal Ca(2+) channel blockers (i.e., GVIA, IVA, furnidipine); and (ii) that combined Ca(2+) channel blockers may provide greater cytoprotection than single compounds.

Pharmacological protection against the cytotoxicity induced by 6-hydroxydopamine and H2O2 in chromaffin cells.

We present in this report the characteristics of the damage induced by 6-hydroxydopamine and H2O2 on bovine chromaffin cells in primary culture. Cytotoxicity was quantified using catecholamine cell contents, lactate dehydrogenase (LDH) release, trypan blue exclusion and morphological appearance. An excellent correlation between these four parameters was found. The cytotoxic effects of 6-hydroxydopamine were Ca(2+)-independent. In spite of this, the Ca2+ channel antagonists R56865 (N-[1-(4-(fluorophenoxy)butyl)]-4-piperidinyl-N-methyl-2-benzo-thiazo lamine) lidoflazine exhibited marked cytoprotective effects against both 6-hydroxydopamine and H2O2. The selective dopamine uptake blocker, bupropion, increased the viability of 6-hydroxydopamine and H2O2-treated cells from 20% to around 80%. Catalase drastically protected against the cytotoxic effects of 6-hydroxydopamine and H2O2. In contrast, desferrioxamine gave better protection against H2O2 cytotoxicity; glutathione and N-acetylcysteine only afforded substantial protection against 6-hydroxydopamine. Three main conclusions emerge from this study. (1st) 6-Hydroxydopamine causes chromaffin cell damage via a mechanism probably related to the production of free radicals, but unrelated to Ca2+ ions. Cytoprotection afforded by R56865 and lidoflazine must be unrelated to their Ca2+ antagonist properties. This suggests a novel component in the cytoprotective mechanism of action of these drugs. (2nd) The strong cytoprotective effects of bupropion seem to be unrelated to its ability to block the plasmalemmal dopamine carrier. (3rd) Bovine adrenal chromaffin cells in primary cultures are a suitable model for adult neurons to study the basic mechanism of cell damage, and to screen new drugs with putative neuroprotective properties.