There is no association between combined oral hormonal contraceptives and depression: a Swedish register-based cohort study.

OBJECTIVE: To investigate whether users of hormonal contraceptives (HCs) are at increased risk of depression compared with non-users. DESIGN: Register-based cohort study. SETTING: Sweden. SAMPLE: Women aged 15-25 years between 2010 and 2017 with no prior antidepressant treatment, psychiatric diagnose or contraindication for HCs (n = 739 585). METHODS: Women with a prescription of HC were identified via the Swedish Prescribed Drug Register (SPDR). Relative risks (RRs) for first depression diagnosis in current HC-users compared with non-users were modelled by Poisson regression. Adjustments included age, medical indication for HC-use and parental history of mental disorders, among others. MAIN OUTCOME MEASURES: Depression, captured by a redeemed prescription of antidepressant treatment, or a first depression diagnosis in the SPDR and the National Patient Register. RESULTS: Compared with non-users, women on combined oral contraceptives (COCs) and oral progestogen-only products had lower or no increased risk of depression, relative risk (RR) 0.89 (95% CI 0.87-0.91) and 1.03 (95% CI 0.99-1.06) after adjustments, respectively. Age-stratified analyses demonstrated that COC use in adolescents conferred no increase in risk (RR 0.96, 95% CI 0.93-0.98), whereas use of progestogen-only pills (RR 1.13, 95% CI 1.07-1.19), contraceptive patch/vaginal ring (RR 1.43, 95% CI 1.30-1.58), implant (RR 1.38, 95% CI 1.30-1.45) or a levonorgestrel intrauterine device (RR 1.59, 95% CI 1.46-1.73) were associated with increased risks. CONCLUSIONS: This study did not find any association between use of COCs, which is the dominating HC in first time users, and depression. Non-oral products were associated with increased risks. Residual confounding must be addressed in the interpretation of the results. TWEETABLE ABSTRACT: There is no association between combined hormonal contraceptives and depression.

Effects on jaw function shortly after whiplash trauma.

Normal jaw function involves muscles and joints of both jaw and neck. A whiplash trauma may disturb the integrated jaw-neck sensory-motor function and thereby impair chewing ability; however, it is not known if such impairment is present shortly after a neck trauma or develops over time. The aim was to evaluate jaw function after a recent whiplash trauma. Eighty cases (47 women) were examined within 1 month after a whiplash trauma and compared to 80 controls (47 women) without neck trauma. Participants completed the Jaw disability checklist (JDC) and Neck Disability Index (NDI) questionnaires and performed a 5-minute chewing test. Elicited fatigue and pain during chewing were noted, and group differences were evaluated with Fisher's exact test and Mann-Whitney U-test. Compared to controls, cases had higher JDC (P < .0001) and NDI scores (15% vs 2%, P < .0001), and reported more fatigue (53% vs 31%, P = .006) and pain (30% vs 10%, P = .003) during the chewing test. Cases also had a shorter onset time for fatigue and pain (both P = .001) Furthermore, cases reporting symptoms during chewing had higher JDC and NDI scores compared to cases not reporting symptoms (both P = .01). Symptoms mainly occurred in the trigeminal area for both groups, but also in spinal areas more often for cases than for controls. Taken together, the results indicate that jaw-neck sensory-motor function is impaired already within 1 month after a whiplash trauma. The association between neck disability and jaw impairment underlines the close functional relationship between the regions, and stresses the importance of multidisciplinary assessment.

Poor Response to Periodontal Treatment May Predict Future Cardiovascular Disease.

Periodontal disease has been associated with cardiovascular disease (CVD), but whether the response to the treatment of periodontal disease affects this association has not been investigated in any large prospective study. Periodontal data obtained at baseline and 1 y after treatment were available in 5,297 individuals with remaining teeth who were treated at a specialized clinic for periodontal disease. Poor response to treatment was defined as having >10% sites with probing pocket depth >4 mm deep and bleeding on probing at ≥20% of the sites 1 y after active treatment. Fatal/nonfatal incidence rate of CVD (composite end point of myocardial infarction, stroke, and heart failure) was obtained from the Swedish cause-of-death and hospital discharge registers. Poisson regression analysis was performed to analyze future risk of CVD. During a median follow-up of 16.8 y (89,719 person-years at risk), those individuals who did not respond well to treatment (13.8% of the sample) had an increased incidence of CVD ( n = 870) when compared with responders (23.6 vs. 15.3%, P < 0.001). When adjusting for calendar time, age, sex, educational level, smoking, and baseline values for bleeding on probing, probing pocket depth >4 mm, and number of teeth, the incidence rate ratio for CVD among poor responders was 1.28 (95% CI, 1.07 to 1.53; P = 0.007) as opposed to good responders. The incidence rate ratio among poor responders increased to 1.39 (95% CI, 1.13 to 1.73; P = 0.002) for those with the most remaining teeth. Individuals who did not respond well to periodontal treatment had an increased risk for future CVD, indicating that successful periodontal treatment might influence progression of subclinical CVD.

Pain and Disability in the Jaw and Neck Region following Whiplash Trauma.

The relationship between whiplash trauma and chronic orofacial pain is unclear, especially with regard to the time elapsed from trauma to development of orofacial pain. The aim was to analyze prevalence of jaw pain and disability, as well as the relationship between pain and disability in the jaw and neck regions in the early nonchronic stage after whiplash trauma. In this case-control study, 70 individuals (40 women, 30 men, mean age 35.5 y) who visited an emergency department with neck pain following a car accident were examined within 3 wk of trauma (group 1) and compared with 70 individuals (42 women, 28 men, mean age 33.8 y), who declined to attend a clinical examination but agreed to fill in questionnaires (group 2). The 2 case groups were compared with a matched control group of 70 individuals (42 women, 28 men, mean age 37.6 y) without a history of neck trauma. All participants completed questionnaires regarding jaw pain and dysfunction, rating pain intensity in jaw and neck regions on the Numerical Rating Scale, the Neck Disability Index, and Jaw Disability Checklist. Compared with controls, individuals with a recent whiplash trauma reported more jaw pain and dysfunction. Furthermore, there was a moderate positive correlation between jaw and neck pain ratings for group 1 (r = 0.61, P < 0.0001) and group 2 (r = 0.59, P < 0.0001). In the logistic regression analysis, cases showed higher odds ratios (range, 6.1 to 40.8) for jaw and neck pain and disability compared with controls. Taken together, the results show that individuals with a recent whiplash trauma report more jaw pain and disability compared with controls without a history of neck trauma. Furthermore, the correlation between jaw and neck pain intensity implies that intensity of neck pain in the acute stage after whiplash trauma might be a possible risk factor also for development of chronic orofacial pain.

Qigong training and effects on stress, neck-shoulder pain and life quality in a computerised office environment.

BACKGROUND: Qigong is a Chinese health promoting exercise with a rhythmic pattern of slow movements and breathing affecting the autonomous nervous system. OBJECTIVES: To examine the implementation of Qigong for half an hour daily in a computerised office, and to study effects on health state, general health, neck-shoulder and lumbar spine symptoms and stress after six weeks training DESIGN: A crossover intervention study with 37 employees randomised in two groups. A questionnaire was completed one week before starting study and every second week during the training period. After 6 weeks the first group stopped and the second group started the training. RESULTS: There was a small significant improvement of neck pain and disability following therapy. CONCLUSION: Qigong training may reduce neck disability in office workers. A longer training period might be needed in further Qigong studies in healthy, normal populations.

[Vincenzo Cuomo, pioneer in thalassotherapy]. / Vincenzo Cuomo, un pioniere della Talassoterapia.

Thermal Medicine is now well integrated with other therapies such as pharmacotherapy, surgery, physiotherapy, radiotherapy and so on, in the prevention, cure and rehabilitation of many diseases. The methodology of thermal treatments, now recognized as bona fide therapies with their specific indications, adverse side effects, dosages, applications and administration times, are classified into mineral baths, mudcures and grotto treatments. Thalassotherapy is a therapy that is linked to the sea and is one of the most important of the climatotherapeutic methods. It constitutes a complex of therapeutic effects derived from the meteorological and telluric factors characterising a given climate. Thalassotherapy deals with the therapeutic effects conferred by periods of time spent by the sea, including the modes of action of marine agents, and strives to determine their limitations and in what circumstances a sojourn by the sea can provide effective health benefits. Thalassotherapy is affected by three kinds of main factors: climatotherapeutic factors, eliotherapeutic factors and balneotherapeutic factors. Refraining from normal daily activities and a rigorous observance of general hygiene, and diet in particular must also always be observed.

A new multiple regression model to identify multi-family houses with a high prevalence of sick building symptoms "SBS", within the healthy sustainable house study in Stockholm (3H).

PURPOSES: The aim was to develop a new model to identify residential buildings with higher frequencies of "SBS" than expected, "risk buildings". METHODS: In 2005, 481 multi-family buildings with 10,506 dwellings in Stockholm were studied by a new stratified random sampling. A standardised self-administered questionnaire was used to assess "SBS", atopy and personal factors. The response rate was 73%. Statistical analysis was performed by multiple logistic regressions. RESULTS: Dwellers owning their building reported less "SBS" than those renting. There was a strong relationship between socio-economic factors and ownership. The regression model, ended up with high explanatory values for age, gender, atopy and ownership. Applying our model, 9% of all residential buildings in Stockholm were classified as "risk buildings" with the highest proportion in houses built 1961-1975 (26%) and lowest in houses built 1985-1990 (4%). CONCLUSION: To identify "risk buildings", it is necessary to adjust for ownership and population characteristics.

Possible antioxidant role of SPA therapy with chlorine-sulphur-bicarbonate mineral water.

The aim of our research was to analyze the antioxidant role and efficacy of thermal or salus per aquam (spa) therapy with chlorine-sulphur-bicarbonate mineral water. The study has been performed on 30 rats. The animals were randomized in three groups, each of them composed by ten animals, denominated A, B and C. The A group was the control group and was not subjected to any specific treatment (placebo); the B group has been treated with a standard cycle of hydropinics treatment with mineral water of Therme of Stabia in Castellammare (Naples, Italy) denominated STABIA; the C group was treated with a standard cycle of hydropinic treatment with mineral water of Therme of Stabia in Castellammare (Naples, Italy) denominated SULFUREA. After two weeks of treatment all the rats were sacrificed and blood was collected for the plasmatic determination of reactive oxygen species (ROS). The results demonstrated a significant (P < 0.05) reduction of ROS in B (374 Carr. U. +/-73) and C group (399 carr. U. +/-62) treated with mineral waters if compared with control group (571 + 69 Carr. U.). In conclusion this study suggests a possible antioxidant effect of chlorine-sulphur-bicarbonate spa hydropinic treatment with a consequent suitable intestinal physiology, with reduction of the functional and organic modifications that can lead to pathological disorders of the gastroenteric diseases in whose pathogenesis the oxidative stress can develop an important role.

Effectiveness of sulphur spa therapy with politzer in the treatment of rhinogenic deafness.

Several studies have focused on the usefulness of sulphur, radioactive and bromo-iodine mineral waters in the treatment of chronic inflammatory lower and upper respiratory processes. The purpose of this study was to evaluate the tolerability, effectiveness and impact on quality of life of sulphur spa therapy with Politzer in subjects with chronic inflammatory processes responsible for the onset or persistence of rhinogenic deafness. The study was performed on 27 subjects (mean age 62 +/- 2.2 years, range: 28-88) with chronic catarrhalis otitis, chronic rhino-sinusitis and pharyngeal inflammation. These patients underwent 12 sessions of humid-hot inhalation, with vapour jet 20 cm from the face, at 38 degrees C for 10 min, followed by Politzer with sulphur sodium chloride bicarbonate alkaline mineral water from "Rosapepe" Spa, in Contursi (Salerno, Italy). Middle ear function and possible social recovery (based on Giaccai and Gardenghi guidelines) of the patients were assessed, at the beginning and end of the spa therapy. Results, at the end of this treatment, showed a significant (p < 0.05) increase in audiometric curves corresponding to the normal ventilation of the tympanic box (incidence of 24% before therapy and 33% thereafter) and a decrease in pathological curves. Moreover, a significant (p < 0.05) reduction in the percentage of auditory loss was recorded (N = 41; 19.7% +/- 2.5 --> 13.9% +/- 1.9) and improved hearing, at the frequencies required for daily activities: 500-1000 and 2000 Hz (31.1 dB +/- 1.7 --> 26.8 dB +/- 1.5). No adverse effects to the spa therapy were observed during the study. In conclusion, the results of this study are in agreement with data in the literature, demonstrating that associated spa therapy with Politzer and inhalation have a positive impact on the therapeutic strategy of chronic inflammatory processes, responsible for the onset or persistence of rhinogenic deafness, in order to enhance and combine with the already consolidated pharmacological approaches.

[Psoriasis and mud bath therapy: clinical-experimental study]. / Psoriasi e fangobalneoterapia: studio clinico sperimentale.

OBJECTIVE: The psoriasis is chronic disease characterized from an acceleration of the kinetic of the cells of epidermis. To front of the empirical evidence of the benefits of the thermal therapy in the psoriasis, the experimentals-clinics studies is insufficient. The aim of research it has been that of quantify the benefits of the mud-bath therapy with mineral water in the psoriasis. PATIENT AND METHODS: The study has been channel on a champion of 30 subjects of which 19 of male sex and 11 of female sex with middle equal age to 56 years +/- 5.3 affected from psoriasis. The subjects of the examined champion have been divided to random in 2 groups: A and B. The group A has been treated with drugs used for psoriasis for 12 days; the B group has been treated, always for 12 consecutive days, with mud-bath therapy (FBT) with mineral water obtained from the mineral sources (chlorinate-sulphureous-bicarbonate) of the Spa of Stabia in Castellammare (NA). To the beginning and at the end of the advised treatments has been valued the prurient symptomatology and the PASI (Psoriasis and Severity Index). RESULTS: The data highlight an significant (P < 0.05) reduction is of the prurient symptomatology and of the PASI in both the groups considered. CONCLUSIONS: The results of this first step of investigations seems to highlight that the FBT treatment, to the same way of the drugs anti-psoriasis, results useful in the ameliorate the quality of life of these patients.

Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice.

The administration of mineral sulphur water is an alternative experimental approach for the treatment of rheumatic diseases, such as osteoarthritis (OA), that cause the degeneration of bone and cartilage and sufferance to the patients. Chondroitin sulfate (CS) is a symptomatic slow acting nutropeucital agent currently used in molecular therapy of OA. Therefore, we have studied the role and efficacy of the selective soil paste from the mineral sulphur enriched spring (mud)-therapy alone or in combination with CS in the treatment of OA. The study was performed on 40 C57 Black 6N mice, an experimental model which spontaneously develop an osteoarthritic process. The animals were divided in 4 groups and were treated with the single agents or with the combination. After 30 days of treatment all the mice were sacrificed and right knees and blood were collected. It was found that CS determined a reduction of radiological and histological features of chondrodegeneration and that mud-therapy increased the effects of CS in the animal group treated with the combination. However, the effects of thermal therapy alone were not statistically significant. Since OA is characterized by an increase of the production of nitric oxide (NO) by chondrocytes in extracellular matrix with its consequent elevation in serum and synovial fluid, we have evaluated the effects of the treatments on serum NO levels. CS alone induced a statistically significant reduction of NO serum levels (90+/-13 micromM vs 219+/-60 microM of control group, P<0.05) while mud-therapy alone induced a not statistically significant reduction of serum NO (170+/-62 microM, P>0.05). However, the latter strongly potentiated the decrease of serum NO induced by CS (31+/-1.5 microM) with a high statistical significance if compared to both the control group (P<0.01) and the CS-treated group (P<0.05). In conclusion, this study demonstrates that mud-therapy with sulphur mineral water could represent an important phase of the therapeutic strategy of OA. This experimental strategy could integrate and potentiate the standard pharmacological tools. Moreover, we have set a valid experimental in vivo model for the study of the thermal effects on the development of OA.

[Inhalation therapy with sulphur water in ORL: clinical-experimental study]. / Cura inalatoria con acqua minerale sulfurea in ambito ORL: studio clinico--sperimentale.

OBJECTIVE: Several clinics and experimental researches have highlighted the utility of the inhalant mineral therapy in numerous diseases to load of the tall and low respiratory streets. Aim of the our clinical-experimental study has been that of appraise "to brief term" the curative effects and the adverse reactions of a thermal inhalant treatment with sulphur water in the care of diseases ORL apparatus (laryngitis, pharyngitis, rhinitis, rhinosynusitis), appraise the course of some End points to distance. PATIENT AND METHODS: The study has been channel on a champion of 83 subjects of which 45 of male sex and 38 of female sex with age serious equal average to 53 years +/- 2.6. The subjects of the examined champion that affections from diseases inflammatory chronic of ORL relevance (laryngitis, pharyngitis, rhinitis) were subjected to a cycle of sulphur mineral inhalant therapy disbursed with businesslike individual of inhalations to bud of vapor to the T of 38 degrees C to 20 cm from the face with duration of 10 min, follows from aerosol for likewise minutes. To the beginning and at the end of the sulphur mineral inhalant cycle has been valued the subjective symptomatology susceptible of amelioration, some End Points to distance and the adverse reactions. RESULTS: The data seem to highlight the end cycle curative sulphur mineral inhalant an significant (P < 0.05) amelioration of best part of the symptoms examined like cough, nasal itch, expectoration [etc]. The analysis of the End Points to advised Distance show an significant (P < 0.05) progressional diminution of such indicators to succession of the annual continuity of the inhalant sulphur mineral treatment. CONCLUSIONS: The results of such research seem to demonstrate that the inhalant sulphur mineral therapy can induced notable benefit in different inflammatory chronic diseases of ORL relevance in peculiar in the first ten of life with a positive relapse on some End Points to distance and an excellent local and systemic tolerable.

Bioequivalence assessment of two different tablet formulations of diltiazem after single and repeated doses in healthy subjects.

The study was performed on 14 healthy volunteers in order to compare the pharmacokinetics and hence assess the bioequivalence of two different tablet formulations of diltiazem administered orally. The study was carried out after single doses (60 mg) and repeated doses (60 mg three times a day for six days and 60 mg on the seventh day) according to a randomised, cross-over, open design. The pharmacokinetic parameters AUC0-infinity (ng h/ml), Tmax(h) and Cmax (ng/ml) were calculated for the two formulations after a single dose, while AUCt1-t2 (= AUC for a repetitive dose interval or dosing cycle, ng h/ml) and PTF (peak trough fluctuation) were calculated after repeated doses. The bioequivalence assessment was the shortest 90% confidence interval for the ratio (difference) of expected medians in the respective bioequivalence range (0.80-1.20). The results of this study show that, after either a single dose or repeated doses of test or reference formulations of diltiazem, the pharmacokinetics of the two formulations are similar. The ratios of AUC on day 1 (for single-dose treatment) and on day 7 (for repeated-dose treatment), and the corresponding 90% confidence intervals demonstrate bioequivalence between the two formulations of diltiazem within the accepted range of 0.80-1.20 (80-120%).

Pharmacokinetics of cefodizime in patients with various degrees of renal failure.

The pharmacokinetics of cefodizime, a new expanded-spectrum cephalosporin for parenteral use, was studied in 45 subjects with various degrees of renal failure. Patients were divided into five groups according to the following creatinine clearances: group I >80 ml/min; group II <80-30 ml/min; group III <30-15 ml/min; group IV <15-5 ml/min and group V <5 ml/min. Cefodizime was administered as a 1 g i.v. bolus. Plasma and urinary concentrations of cefodizime were determined by high-performance liquid chromatography, using for detection UV absorbance. The following pharmacokinetic parameters were calculated: maximum plasma concentration (C5 min), area under the plasma concentration-time curve (AUC), terminal half-life (T1/2), terminal rate constant (lambda-z), total clearance (Clt), volume of distribution (Vd), mean residence time (MRT), urine data-derived terminal half-life (T1/2 r), renal clearance (Clr). The results of this study showed that renal failure induced changes in cefodizime pharmacokinetics. Our data demonstrated a close correlation between degree of renal impairment and pharmacokinetic changes. The maximum plasma concentration (C5 min) was higher in patients with renal failure; T1/2 was increased; AUC also increased from 470.40 +/- 17.80 mg.h/l in the control group to 1,562.30 +/- 170.8 mg.h/l in group V. Moreover, no side effect was observed after treatment with 1 g i.v. of cefodizime. Although renal failure induces significant changes of cefodizime pharmacokinetics, the drug was well tolerated and only in patients with severe renal insufficiency we advise to monitor the interval dose of cefodizime or adjust doses to renal function.

Synthesis of 1-methyl-4-(N-aroyl)-piperidinamides with anti-inflammatory and analgesic activities.

Two series of 1-methyl-4-(N-aroyl)-piperidinamides were synthesized and evaluated for their anti-inflammatory and analgesic properties, as well as for their gastrointestinal irritation liability. A non-aromatic derivative, 1-methyl-4-(N-cyclohexanoyl)-piperidinamide, was synthesized and evaluated in order to obtain a more exhaustive knowledge of the structure-activity relationship.

Bioavailability of timolol and aceclidine after ocular instillation in the rabbit.

The bioavailability of timolol and aceclidine after the ocular instillation of each drug (timolol 0.5% or aceclidine 2%) or both combined (timolol 0.5% + aceclidine 2%) has been evaluated in rabbits. 15 male albino rabbits were treated by the instillation of timolol and aceclidine alone or combined in the conjunctival sac of the right eye. Timolol concentrations in humor aqueous were assayed at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 6 hr after instillation by high-performance liquid chromatography (HPLC). Aceclidine was assayed by a pharmacodynamic method: pupillary diameter at the following time intervals 0 (basal value), 1 min, 5 min, 30 min, 1 hr, 2 hr, 4 hr, 6 hr after treatment. Our results demonstrated that no differences in timolol and aceclidine bioavailability were found between simple-drug preparations and their combination.

[Problems associated with the use and monitoring of cyclosporin. Experience at a Clinical Pharmacology Service]. / Problematiche connesse all'uso e al monitoraggio della ciclosporina. Esperienza di un Servizio di Farmacologia Clinica.

BACKGROUND: A study on cyclosporine A (CyA) monitoring in the January 1992-December 1995 period is reported. The aim of this work was to give epidemiological data on the use of CyA, to verify the progressive increase of CyA determinations and to evaluate the use in other diseases as well as to compare the different technics of CyA assay in blood samples, to stress the timing of blood samples and to underline the CyA monitoring importance. METHODS: The CyA dosage was evaluated by fluorescence polarization immunoassay (FPIA) and high-performance liquid chromatography (HPLC). RESULTS: The study showed that 70% of CyA determinations come from patients undergone to renal, bone marrow and liver transplantations; the remaining 30% was associated to other diseases (psoriasis, uveitis, diabetes, rheumatoid arthritis). CONCLUSIONS: The results obtained showed a progressive and constant increase of CyA determinations. Moreover, the use of drug was increased in autoimmune diseases. It is stressed that CyA monitoring in blood samples is essential to optimize the therapeutic efficacy of drug and minimizing its toxicity.

Effect of atenolol and ramipril on regression of left ventricular hypertrophy: comparative echocardiographic assessment.

Left ventricular hypertrophy (LVH) dramatically worsens hypertensive illness. Because the genesis of LVH appears to be multifactorial, antihypertensive treatment should aim to reduce not only pressor values but also the hypertrophic ventricular mass. This result can be obtained only when drugs able to act on both pathogenetic factors are used. To evaluate the effectiveness of antihypertensive therapy on regression of LVH, 21 patients with stage 2 essential hypertension were treated for a year with either atenolol (120 mg/d orally), a cardioselective beta-blocker without intrinsic sympathomimetic activity, or ramipril (5 mg/d orally), an angiotensin-converting enzyme inhibitor with high tissue activity. Both treatments produced significant control of hypertension and regression of LVH. No statistically significant difference between treatments was noted, except for heart rate, which was substantially unchanged by ramipril but significantly decreased by atenolol. Both drugs were well tolerated. Atenolol and ramipril have a major role in the long-term treatment of hypertension and in the regression of hypertension-associated LVH.

Synthesis and pharmacological activities of ethyl 5-cyano-1,6-dihydro-6-oxo-2-(2,3,4-pyridyl)-3-pyridinecarboxylates and derivatives.

The synthesis of ethyl esters of 5-cyano-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids carrying as 2-substituent the 2-,3- or 4-pyridyl group is described. By alkaline hydrolysis followed by acidification, these esters gave the corresponding carboxylic acids, which were decarboxylated to 1,2-dihydro-2-oxo-6-(2,3,4-pyridyl)-3-pyridinecarbonitriles. As milrinone analogues, the above compounds were tested on contractile activity and frequency rate of spontaneously beating atria from reserpine-treated guinea-pigs. Ethyl 5-cyano-1,6-dihydro-6-oxo-2-(2-pyridyl)-3-pyridinecarboxylate showed an appreciable positive inotropic activity, although inferior to that of milrinone; moreover, some other compounds bearing the above 2-substitution pattern showed interesting antiinflammatory, analgesic and hypotensive activity.