Histamine and calcium secretion in the submandibular gland of the cat evoked by two types of stimulation

The aim of this work was to compare the pools of histamine and calcium in the submandibular gland of the cat during two kinds of stimulation of the gland. Submandibular glands of the cat were stimulated electrically (chorda tympani nerve) and by close arterial infusion of pilocarpine. Each stimulation was adjusted in such a way as to obtain a near maximal secretory response. Concentrations of histamine and calcium were measured in nonstimulated and stimulated glands, in saliva, secreted during stimulation and in the venous outflow from the gland before and during the stimulation. The experiments showed that: pilocarpine stimulation lowered the histamine concentration in the gland more than electrical stimulation of the chorda tympani nerve. Calcium stores in the gland were depleted to the same extent by each type of stimulation. the concentration of histamine and calcium in the saliva produced by close arterial pilocarpine infusion was significantly higher than in the saliva secreted during nerve stimulation. histamine and calcium concentrations were higher in the venous outflow from stimulated glands than before stimulation. The results indicate a close relationship between histamine and calcium in salivary secretion, although the origins of the two substances are different.     

Normothermic and hypothermic models for studying the deleterious effects of hypoxia-reoxygenation on EDHF-mediated relaxation in isolated porcine coronary arteries

IntroductionThe vasomotor response of the coronary artery is altered by hypoxia–reoxygenation (H–R) induced damage. The aim of our study was to compare and evaluate normothermic and hypothermic models which are suitable for future drug studies of vasoprotective action against H–R injury.MethodsPorcine coronary arterial rings were isolated and placed in Krebs–Henseleit (K–H) solution. Rings were exposed to normoxic conditions (control group) and two different H–R conditions: the first induced by a 95% N₂–5% CO₂ gas mixture (40- and 60-min hypoxia) in a normothermic protocol, and the second induced by hypothermic (4 °C) hypoxia–reoxygenation in an air-tight beaker filled with K–H solution (24- and 48-hours hypoxia). Reoxygenation was applied by introducing K–H solution aerated with a 95% O₂–5% CO₂ mixture under normothermic (37 °C) conditions. To test the EDHF-mediated relaxation by substance P, rings were first incubated in L-NNA, nitric oxide synthase inhibitor, and indomethacin, cyclooxygenase inhibitor, and then pre-contracted with thromboxane analogue U-46619. Analysis of the maximum relaxation of the arterial rings was performed by one-way ANOVA, followed by Bonferroni's post-test.ResultsDistal segments of the coronary artery responded faster to contraction induced by U-46619 and were relaxed by substance P to a greater extent than proximal segments. Maximal relaxations of arterial rings induced by a 10 nM solution of substance P were significantly reduced (p < 0.001) from the values for normoxic rings (81.0 ± 1.0%, n = 30) after 40-min H–R (50.5 ± 5.3%, n = 30), 60-min H–R (32.1 ± 3.5%, n = 30), 24-hours hypothermic H–R (56.0 ± 2.3%, n = 30) and after 48-hours hypothermic H–R (38.5 ± 5.1%, n = 30).ConclusionsThe model employing 40-min normothermic H–R is as effective as 24-hours hypothermic H–R, and 60-min normothermic H–R as 48-hours hypothermic H–R for studying the deleterious effects of H–R on EDHF-mediated relaxation.     

Tricyclic antidepressants change plasma histamine kinetics after its secretion induced by compound 48/80 in the rat

Inflammation Research -     

The inhibition of salivary secretion by histamine H2-antagonists--a study on the cat submandibular gland

The aim of the present work was to establish whether the secretory process can be influenced by histamine H2-receptor antagonists, burimamide and metiamide. These drugs were applied intravenously and the secretion was evoked by the electrical stimulation of the chorda tympani nerve or by carbachol (i.v.). In addition to the measurements of the flow of saliva, the blood flow through the gland was measured in some experiments. Both H2-antagonists significantly reduced the rate of salivary secretion induced by the chorda tympani stimulation. The experiments with burimamide did not permit the calculation of dose-response relationship. From the experiments with metiamide the ED50 was 4.6 mumols/kg and Emax was 30% reduction of secretion. The secretory response to carbachol was not diminished by burimamide. In addition to the effect of metiamide on salivation, the reduction of the blood flow through the gland was observed: the effect on the blood flow was significantly smaller, and slower in onset, than the effect on salivation. These results support the hypothesis that H2-receptors are involved in the process of salivary secretion. Histamine effects on glandular elements seem to be more significant than its effect on the blood vessels.     

The effect of compound 48/80, substance P and pentagastrin on the isolated guinea pig atrium

It has been shown that histamine is present in guinea pig hearts. In the present work, the effect of some substances, known to liberate mast cell histamine, on the isolated guinea pig atria was studied. Compound 48/80 (100 g/ml), pentagastrin (10^–6 M) and substance P (10^–5 M) were added 2–3 times to the isolated organs and the frequency of contractions was measured. At the end of experiments, the atria were examined histologically for mast cell degranulation.Compound 48/80 and pentagastrin increased the frequency of contractions of isolated atria. Substance P provoked a dose-dependent decrease of contraction frequency; this effect was diminished by atropine (10^–5 M). All three substances provoked pronounced degranulation of mast cells present in the atrium, the effect of substance P being significantly greater than the effects of the other two substances. It can be concluded that mast cells, present in guinea pig atrium, are sensitive to the histamine liberators used; histamine is released in quantities high enough to produce an effect.     

Continuous decompression of unicameral bone cyst with cannulated screws: a comparative study

We determined the role of mechanical decompression in the resolution of unicameral bone cyst. A total of 69 children with unicameral bone cysts were treated either by (i) open curettage and bone grafting, (ii) steroid injection or (iii) cannulated screw insertion. During a mean follow-up of 69 months (range, 12-58), the cysts were evaluated by radiological criteria. The healing rates in the three groups were 25, 12 and 29% after the first treatment, and a further 50, 19 and 65% after the second. The study has demonstrated the advantages of the decompression technique for unicameral bone cysts over other treatment modalities studied.     

Minor head trauma and isolated unilateral internuclear ophthalmoplegia

Internuclear ophthalmoplegia is a syndrome that develops due to a lesion of the medial longitudinal fasciculus. This lesion is mostly caused by multiple sclerosis (usually bilaterally), and only rarely by head injury. A case is presented of unilateral internuclear ophthalmoplegia as an isolated sequel of minor head trauma, which eventually resolved. A 40-year-old woman with isolated internuclear ophthalmoplegia secondary to closed head trauma with anatomical lesions of the mesencephalon in the region of medial longitudinal fasciculus is described. A minor contusion was detected by magnetic resonance imaging. Diplopia resolved in 5 months. In conclusion, internuclear ophthalmoplegia should be considered in the differential diagnosis in patients with recent head injuries showing adduction impairment. The connection between the clinical picture and anatomical lesions is visualized by magnetic resonance imaging.     

Acute effects of a low‐dose atropine/scopolamine mixture as a food contaminant in human volunteers

To verify the assumptions in our previous risk assessment of an atropine/scopolamine mixture in buckwheat flour, we performed a randomized, double‐blind, placebo‐controlled cross‐over study in 20 healthy, adult volunteers. The volunteers ingested a traditional Slovenian buckwheat meal, made of boiled buckwheat flour to which alkaloids were added. In addition to the placebo they ingested 0.12/0.10, 0.37/0.29, 1.22/0.95, 3.58/2.81 and 12.10/9.50 µg kg^–1 body mass (BM) of the atropine/scopolamine mixture. The changes in body temperature, heart rate, salivary and sweat secretion, pupil size, near‐point vision and subjective symptoms were recorded regularly for 4 h after the ingestion. Decreased salivary and sweat secretion, increased heart rate and pupil size and reduced near‐point vision accompanied by characteristic subjective symptoms were observed at 12.10/9.50 µg kg^–1 BM. At doses of 0.37/0.29 and 1.22/0.95 µg kg^–1 BM, a significant decrease in the heart rate was noted, which we consider to be a critical effect of a low‐dose exposure to the atropine/scopolamine mixture. Although this did not have any clinical relevance in our subjects, it may have serious implications if it occurred in people with pre‐existent cardiac conditions or those on medications that may cause bradycardia. No significant changes in the observed end points were noted at 0.12/0.10 µg kg^–1 BM. We estimate that the NOAEL (No Observed Adverse Effect Level) for the atropine/scopolamine mixture lies between the lower two administered doses. Applying the uncertainty factor of 10, we propose a new provisional Acute Reference Doses (ARfDs) of the mixture, i.e. 0.01 µg kg^–1 BM for each alkaloid, and a further refinement using higher‐tier approaches. Copyright © 2012 John Wiley & Sons, Ltd.     

Emerging Trends in the Epidemiology of COVID-19: The Croatian ‘One Health’ Perspective

During the four pandemic waves, a total of 560,504 cases and 10,178 deaths due to COVID-19 were reported in Croatia. The Alpha variant, dominant from March 2021 (>50% of positive samples), was rapidly replaced by Delta variants (>90%) by August 2021. Several seroprevalence studies were conducted in different populations (general population, children/adolescents, professional athletes, healthcare workers, veterinarians) and in immunocompromised patients (hemodialysis patients, liver/kidney transplant recipients). After the first pandemic wave, seroprevalence rates of neutralizing (NT) antibodies were reported to be 0.2–5.5%. Significantly higher seropositivity was detected during/after the second wave, 2.6–18.7%. Two studies conducted in pet animals (February-June 2020/July–December 2020) reported SARS-CoV-2 NT antibodies in 0.76% of cats and 0.31–14.69% of dogs, respectively. SARS-CoV-2 NT antibodies were not detected in wildlife. Environmental samples taken in the households of COVID-19 patients showed high-touch personal objects as most frequently contaminated (17.3%), followed by surfaces in patients’ rooms (14.6%), kitchens (13.3%) and bathrooms (8.3%). SARS-CoV-2 RNA was also detected in 96.8% affluent water samples, while all effluent water samples tested negative. Detection of SARS-CoV-2 in humans, animals and the environment suggests that the ‘One Health’ approach is critical to controlling COVID-19 and future pandemics.     

The Emergence of SARS-CoV-2 within the Dog Population in Croatia: Host Factors and Clinical Outcome

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog populations. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralising antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Due to the retrospective nature of this study, samples for viral isolation and PCR were unavailable. Still, seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.