Histamine-like Substance Research Articles

Justification of the effectiveness of hirudotherapy in dentistry

This article provides a systematic review of studies on the composition of leech saliva secretions, the method of hirudotherapy, and the results of hirudotherapy in complex treatment. The following databases were used to search for the study: Scopus, Web of Science, MedLine, and Global Health. When using known methods of treatment, there is often no stability of results, this is explained by the search for new drugs and methods for treating periodontitis. It is known that the secret of the salivary glands of the medical leech contains more than 100 biologically active substances. The therapeutic effect of hirudotherapy is associated with the mechanical discharge of blood flow and the action of a complex salivary gland secretion of a medical leech. The molecules that exist in leech saliva and are the most studied to date include active substances such as hyaluronidase, hirudin, Kalin, destabilase, bdellins, histamine-like substances, hirustazine, factor XA inhibitor, and collagenase. It is scientifically proven that hirudotherapy leads to a significant improvement in the clinical condition of periodontal tissues, is simple, accessible, and can be recommended for use in the practice of periodontists.

Studies on the quality of liver extract preparations

Result of analyses of different brands of Liver Extract have been presented. It has been recommended that in regard to the 'B12' content the higher limit should be fixed at 150 percent of claim. Total solids' and 'Protein Nitrogen' have not been found to bear any relationship either between themselves or with the contents of 'B12' vitamin and 'histamine like substances' respectively. It has therefore been recommended that these standards should be further investigated. A content of 'histamine-like substances' higher than 50 mcg/ml has been shown to be related with toxicity of the preparation. It has been recommended that standards in relation to the 'toxicity test' and 'limit' of histamine like substances' should be finally arrived at after further collaborative work. A dose of 1.0 ml/Kg rabbit weight has been recommended for Pyrogen Test; a pH range of 5 to 7 has been confirmed.

Hirudotherapy /Leech therapy: Applications and Indications in Surgery

Hirudotherapy (HT) is the application of medicinal leeches (Hirudo medicinalis) for therapeutic use. It is one of the oldest remedies, being employed by various medicinal practitioners. HT involves the attachment of cultured leeches onto the affected areas. Leech therapy involves an initial bite, which is usually a painless bite, followed by the sucking of 5 and 15 ml of blood. Its major therapeutic benefits are not only due to blood sucked during the biting, but also from the various bioactive substances, such as Hirudin, calin, Hyaluronidase, and Histamine-like substances, to name a few. HT has been employed in various disease conditions and surgical complications. It has been successfully used in plastic and reconstructive surgeries, cardiovascular complications, varicose veins, hemorrhoids and various joint ailments. Nowadays, it is also being utilized in gastrointestinal disorders, dermatology and gynecological abnormalities. More recently, HT has found new applications in cancer therapy, hypersensitivity conditions, like asthma, male/female sterility and diabetes. Taking into consideration all the facts, HT efforts should be made in optimizing the success of medicinal leech therapy in clinical and private practice.

A Scombroid Poisoning Causing a Life-Threatening Acute Pulmonary Edema and Coronary Syndrome in a Young Healthy Patient

Scombroid poisoning, also called histamine fish poisoning, is an allergy-like form of food poisoning that represents one of the major problems in seafood safety. It consists in a clinical syndrome associated with consumption of fish and, less frequently, cheese containing high levels of histamine [1, 2]. Usually certain families of dark meat fish are involved, mainly Scombroidae and Scomberesocidae (e.g., tuna, mackerel, skipjack, Bonito, and Cero). Other nonscombroid fish (e.g., mahi—mahi, herring, anchovies, sardines, Australian salmon, swordfish) was also reported to be associated with scombroid fish poisoning [1–5]. High fish histamine concentrations have been found responsible for this kind of poisoning. Histamine and histamine-like substances are generated from histidine by a decarboxylase activity of bacteria such as Proteus, Klebsiella, Aerobacter, Serratia, Enterobacter, and Escherichia coli [6, 7]. The presence of this bacteria and the massive histamine production detected in the fish is usually secondary to contamination of handlers and improper refrigeration [7]. The clinical presentation is generally characterized by flushing, rash, swelling of face or tongue, sweating, headache, dizziness, abdominal cramps, diarrhea, nausea, vomiting, palpitations, respiratory distress, and hypotension. The onset of symptoms generally occurs few minutes after ingestion of contaminated food. Usually the course is selflimiting and antihistamines can be used to relieve symptoms. We report a rare case of a life-threatening scombroid poisoning with myocardial ischemia and acute pulmonary edema after tuna ingestion.

Vestibular Compensation in the Cat: The Role of the Histaminergic System

Histamine is thought to be involved in the recovery of vestibular function as histaminergic medications are effective in vestibular-related syndromes. We conducted studies in the cat to assess the effects of betahistine (a histamine-like substance) on the behavioural recovery process after unilateral vestibular neurectomy (UVN). We also investigated histamine immunoreactivity changes in the vestibular and tuberomammillary nuclei of betahistine-treated lesioned cats compared with untreated and unlesioned cats. Betahistine strongly accelerated the behavioural recovery process after UVN, with a time benefit of approximately 2 weeks for both static posture (support surface) and dynamic equilibrium function (locomotor balance) compared with untreated animals. A bilateral decrease in histamine immunoreactivity was seen in both acute and compensated UVN cats; this effect was strongly accentuated with betahistine treatment. In conclusion, the results indicate that vestibular lesion reduces histamine staining due to an increase in histamine release in the vestibular and tuberomammillary nuclei that promote vestibular recovery. Betahistine dihydrochloride should contribute to this process by acting on both the presynaptic histamine H 3 and postsynaptic histamine H 1 receptors.

Effects of Betahistine Metabolites on Frog Ampullar Receptors

Previous studies have demonstrated that betahistine, an histamine-like substance used widely as an anti-vertigo drug, can decrease ampullar receptor resting discharge without affecting their mechanically evoked responses. Pharmacokinetic studies have shown that this drug is transformed, mainly at the hepatic level, into aminoethylpyridine (M1), hydroxyethylpyridine (M2), then excreted with the urine as pyridylacetic acid (M3). The goal of the present study was to investigate whether betahistine metabolites are also able to affect vestibular receptor activity. Results demonstrated that, in the range tested (10(-7)-10(-2) M), M2 and M3 exerted no effect, whereas M1, at concentrations higher than 10(-6) M, was able to reduce the resting discharge of ampullar receptors without affecting the evoked responses. M1 therefore exerts effects similar to those of betahistine on ampullar receptors. This might be of some clinical interest. On the basis of our data, the hypothesis may be put forward that the anti-vertigo action of betahistine is at first achieved by betahistine itself and then sustained by M1.

Betahistine increases vestibular blood flow

Betahistine is used for treatment of several vestibular disorders. Despite the accepted use of this histamine-like substance, its mechanism of action is not well understood. The purpose of this study was to assess the possibility that one of the activities of betahistine is increasing blood flow in the peripheral vestibular end organs. Using a novel surgical approach, we identified the posterior semicircular canal ampulla of guinea pigs and placed a laser Doppler probe in position to obtain blood flow measurements from the posterior semicircular canal ampulla. Blood pressure, heart rate, and vestibular blood flow were continuously recorded. Concentration-response curves were obtained for betahistine (2.5, 5, 7.5, and 10 mg/kg) and control-vehicle (0.15 mol/L NaCl) infusions. A separate group of subjects was pretreated with the competitive selective H3 agonist, thioperimide maleate, before betahistine treatment. Increases in vestibular blood flow and decreases in blood pressure were observed in response to betahistine infusions. Pretreatment with thioperamide maleate abolished these changes at low doses of betahistine and attenuated the responses at higher doses of betahistine. These results show that betahistine administration induces increases in vestibular blood flow. These findings support the potential use of betahistine for treatment of vestibular disorders, which may be caused by compromised circulation. (Otolaryngol Head Neck Surg 1999;120:400-5.)

Betahistine Dihydrochloride Treatment Facilitates Vestibular Compensation in the Cat

Unilateral lesion of the vestibular system induces posturo-locomotor deficits that are compensated for with time. Drug therapy is currently used to improve the recovery process and to facilitate vestibular compensation. Betahistine dihydrochloride is an histamine-like substance that has been employed in vestibular pathology; it was found effective in many forms of vertigo and in vestibular-related syndromes. Investigations performed in animal models have shown betahistine-induced neuronal modulations in the vestibular nuclei complex and interactions with the H1 and H3 histamine receptors. Potentially, this substance is therefore capable to interfere with some recovery mechanisms and to improve the behavioral adaptations. But there is at present a total lack of data concerning the influence of betahistine treatment on vestibular compensation in animal models. The aim of this study was to understand the pharmacological activity of betahistine in the restoration of posture and locomotor balance functions in unilateral vestibular neurectomized cats. Posture recovery was assessed by quantifying the surface reaction of the cat's support as measured while standing erect on its four legs, at rest. Locomotor balance recovery was determined using the rotating beam test, by measuring the maximal performance (max. P.) of the cat and its locomotion speed regulation during the postoperative time period. We have compared the recovery profile and time course of these static (posture) and dynamic (equilibrium) functions in three groups of cats. Two experimental groups were treated at daily doses of 50 mg/kg and 100 mg/kg, respectively. Betahistine dihydrochloride was given orally until complete recovery of posturolocomotor functions. One untreated control group served as the reference. Results showed that postoperative treatment strongly accelerated the recovery process in both treated groups, inducing a time benefit of around 2 weeks as compared to the controls. Maximum performance of the cats on the rotating beam as well as locomotion speed regulation were highly correlated to the postoperative development of the cat's support surface, indicating that compensation of the static vestibulospinal deficits conditioned the subsequent locomotor balance recovery. These behavioral data showed that betahistine dihydrochloride constitutes a useful drug therapy for the symptomatic treatment of central vestibular disorders in our animal model of unilateral vestibular lesion. Improvement of vestibular compensation under betahistine postoperative treatment, as evidenced here for the posture and locomotor balance functions, is discussed both in terms of aspecific effect (histamine-induced increase of the level of vigilance) or more direct action in the vestibular nuclei (histamine-induced rebalance of neuronal activity on both sides).

Epidemic dermatitis due to contact with a moth in Cozumel, Mexico.

In early December 1989, an outbreak that was initially thought to be scabies was investigated among employees of tourist hotels in Cozumel, Mexico. Of 417 employees interviewed, only 19 (4.6%) met a case definition for scabies dermatitis, while 91 (21.8%) reported a nonspecific dermatitis of less than one-week's duration. Persons with nonspecific dermatitis related the onset of their dermatitis to skin contact with a moth that had been present in large numbers in November. At the time of the initial investigation in December, there were no active cases of dermatitis and the moth was no longer present. During early January 1990, numerous cases of dermatitis again began to be reported. Using a case definition for nonspecific dermatitis, a survey of Cozumel's resident population showed an attack rate of 12.1%. A case-control study revealed the only significant risk factor to be skin contact with the suspect moth (P less than 0.01), which had returned in large numbers. Six health workers volunteered to have the moth rubbed on their skin; within 5 min, five of six developed an intense pruritus followed by an erythematous rash. The moth was classified as Hylesia alinda Druce. This species has nettling hairs on its abdomen that excrete a histamine-like substance. Although this moth is normally present in small numbers in Cozumel, the passage of hurricane Gilbert killed most of its natural predators (wasps and bees), allowing its population to overgrow. No control measures were undertaken because the moth's natural predators returned that spring and dramatically reduced the moth population. No further outbreaks of dermatitis occurred.

Studies on the histamine-like substance releasing activity of the peptidoglycan fraction extracted from streptococcal cell walls (author's transl)

Studies on the histamine-like substance releasing activity of the peptidoglycan fraction extracted from streptococcal cell walls (author's transl)

Some properties of the crude extract of scorpion telsons' from Heterometrus gravimanus and presence of acetylcholine- and histamine-like substances.

The lyophilized crude scorpion venom from Heterometrus gravimanus was administered to anesthetized cats, and the changes in electrocardiogram, hypotensive effect, increase in the depth of respiration and blood flow were observed. From the pharmacological experiment on isolated guinea pig ileums, the presence of both acetylcholine-and histamine-like substances was suggested in the crude venom. Acetylcholine-like substance was compared with an authentic acetylcholine on the silicagel thin-layer chromatography, and the amount was estimated to be 8-15 μg equivalent to acetylcholine per mg venom by the Magnus method. Histamine-like substance was extracted and purified from the crude venom, and was run on both silicagel and polyamide thin-layer chromatographies concurrently with an authentic histamine and 5-hydroxytryptamine. By both bioassay with isolated guinea pig ileum and chemical determination with the fluorometric methods, the content of histamine-like substance was calculated to be about 30 μg equivalent to histamine per mg venom. 5-Hydroxytryptamine was not found. Hemolytic action was observed in the human erythrocytes with the venom and the maximal action was found at pH 5.5.

Pain transmission and associated mechanisms

Pain transmission and central control mechanisms have evoked considerable interest in recent years. Extensive research has been and is being done into the subject, and the following three articles written by D. Bowsher, J. M. Mumford and F. T. Monks, who have had a long standing interest in this field, review the present concepts and cover, to some extent, the ideas of recent years that have led up to the present understanding of the subject. Dental pain, its production and the early part of its path o f transmission, is still a matter that is ill-understood. Both J. M. Mumford and F. T. Monks in their papers indicate this difficult problem from differing stand points. Is any part of the dentine innervated or not? Fearnhead and Lumsden (1956) and Fearnhead (1961) in their work on the innervation of teeth used a staining technique for nerve fibres on mature teeth. Their stain was based on silver nitrate which is notoriously capricious and must raise the problem of reliability. Monks (1951) used a silver protein compound, having first assessed its reliability, in a series of elegant histological investigations and came to the conclusion that nervous tissue was not present in the primitive pulp until after odontogenesis was firmly established and felt that under such circumstances it is unlikely for nervous tissue to be subsequently trapped in the advancing calcified dentine. Anderson (1976), in considering the transmission of stimuli across dentine regards the hydrodynamic theory of transmission as highly questionable considering the variable flow rates induced in dentinal tubules by a variety ofiso-osmotic solutions. Yet it is acknowledged that freshly cut dentine in the presence of a normal pulp is surprisingly insensitive. Sensitivity of dentine appears to be associated with pulpal oedema, yet it has not been emphasised that as the pulp is enclosed in a rigid box, and when under pressure, as in situations of oedema, it is likely that although a minimal fl0w of fluid in a tubule will produce a small stimulus at a receptor, the threshold level may be so lowered, it will result in the excitation of the afferent nerve. The fact that different iso-osmotic solutions give different flow rates in dentinal tubules would appear to be irrelevant in conditions of oedema but may be significant for their variable effect on the normal pulp. Speed of conduction across dentine is impressive clinically. Mechanical stimulation would produce a pressure wave in the tubules (rigid walled tubes) travelling at a speed of about 17 metres per second (Bradley, 1976) which is approximately the speed of conduction in a C pain fibre. Even if nervous tissue did penetrate the dentine to some extent, as Mumford suggests, the relationship of the odontoblast and its process with the nervous system is still not known. Would it be too far fetched to consider that the odontoblast and its process is a mechano-receptor and the afferent nerves merely synapse with the surface of the odontoblast in the predentine layer ? Or is the process a pressure effect in the pulp mediated by the liberation of a histamine-like substance as Monks suggests in his article. Recent work by Kollar and Lumsden (1979) suggests very early innervation of the pulp, contrary to Monks (l 951) findings who did demonstrate, however, early innervation of the follicle and sub-epithelial layer. The answers to many of these questions are still awaited, but reading these articles makes one feel that we are a little nearer the truth than we were: teeth are peculiar structures anatomically, embryologically and to some extent, physiologically.

Blood flow in the rabbit tracheal mucosa under normal conditions and under the influence of tracheal intubation.

Isotope labelled microspheres were used to study the capillary blood perfusion of the rabbit tracheal mucosa. Under resting conditions the perfusion was about 0.3 ml/min - g (i.e. about 60% of the relative cerebral blood flow). Irritation of the tracheal mucosa by an endotracheal tube caused a steep rise in blood flow, tenfold or more. This was probably due to relaxation of the arterioles caused by a release of histamine-like substances. When an endotracheal tube is equipped with a small cuff (small resting diameter, low residual volume), the part of the mucosa in contact with the cuff, i.e. the mucosa covering the surface and edges of the cartilages, will be ischaemic at a cuff to tracheal wall pressure (C-T pressure) of greater than 30 millimeters of mercury. This abrupt ischaemia threshold contributes to the risk of deep mucosal damage with subsequent tracheal scarring, possibly proceeding to stenosis. Our present studies indicate that the ideal large cuff, with properties resembling those of an air cushion, will allow the major part of the arterial pressure to be propagated as far down as the capillaries. Under these conditions the cuff would permit some of the capillary blood perfusion of the tracheal mucosa covering the cartilages also at C-T pressures exceeding 30 mmHg. Although this investigation supports the concept that the ideal thin-walled large cuff interferes much less with the mucosal blood perfusion than the small cuff, we recommend that the cuff pressure be monitored and kept below 20 mmHg.

Pharmacological studies with scorpion ( Palamneus gravimanus) venom: evidence for the presence of histamine

The venom from the scorpion Palamneus gravimanus caused, in cats, a pronounced hypotensive effect which was blocked by mepyramine. The hypotensive effect was observed in spinal and reserpinized cats, was not affected by carotid sinus and body denervation and bilateral vagotomy, and was not blocked by hexamethonium and atropine treatment. The venom produced hypertension in guinea pigs and rats which was blocked by tolazoline and in the case of the guinea pigs by mepyramine and by phenoxybenzamine in the rats. Treatment of rats with compound 48/80 did not prevent the hypertensive effect of the venom, showing that it is probably due to histamine or histamine-like substance in the venom and not due to releasing of histamine. Dialysis greatly attenuated the hypotensive effect and prevented the hypertensive action of the venom. Histamine in the venom was identified by paper chromatography, and biological assays showed a histamine-like activity corresponding to 5–7.2 μg histamine per mg dry venom. Both the crude and the dialysed venoms produced positive inotropic and chronotropic effects on isolated rabbit's heart that were not affected by pyribenzamine but were blocked by propranolol. The cardiac stimulant effect of the venom was absent in reserpinized hearts. It is concluded that histamine or histamine-like substance is present in P. gravimanus venom; however, all of the venom effects are not due to the presence of that substance.

Cardiac glycosides (heart poisons) in the polka-dot moth Syntomeida epilais Walk. (Ctenuchidae: Lep.) with some observations on the toxic qualities of Amata (=Syntomis) phegea (L.).

Syntomeida epilaissequesters and stores several cardiac glycosides from its food plantNerium oleanderL. Unlike the other insects previously examined which feed on oleander, this moth stores oleandrin in its body tissues.Amata phegea, feeding on non-poisonous plants, contains a histamine-like substance which increases capillary permeability in rats. Both species are repellent to many avian predators. The predilection shown by several Ctenuchids, and the related Arctiids, for foodplants containing cardiac glycosides or pyrrolizidine alkaloids is discussed.

Histamine and histamine-like substances in the marine sponge, suberites inconstans

1. 1. The tropical sponge, Suberites inconstans, has been shown to contain an appreciable quantity of histamine (31 nmoles per g. wet weight). 2. 2. It also contains lesser amounts of 5 other compounds, which behave like histamine when tested on the guinea-pig ileum but have different R F values on paper chromatograms. Three of these 5 compounds possess phenolic groups in their structures.

Effects of histamine on the toad spinal cord.

THERE is increasing evidence that histamine is a transmitter substance in the central nervous system1–4. In particular, observations suggest that histamine has a synaptic function in the vertebrate spinal cord. The compound is present in sensory nerves of the cat and is liberated peripherally on antidromic stimulation of dorsal roots5. Histamine applied microelectrophoretically can hyperpolarize feline spinal neurones6. Hausler and Sterz7 have reported that histamine enhances spinal reflexes in the frog and that a histamine-like substance is released from the spinal cord when sensory nerves are stimulated, but Angelucci8 was unable to detect an effect of histamine on, or a release of a histamine-like factor from, the frog spinal cord. I have therefore studied the effects of histamine on the isolated spinal cord of the toad, which is a convenient preparation for studying the actions of drugs on nervous tissue.

Colistinおよびその誘導体によるHistamine様物質の遊離

The effects of colistin salts and its derivatives, such as colistin sulfate (C-S), colistin tartrate (C-T), colistin pantothenate (C-P) and sodium colistin methanesulfonate (C-M), on the blood pressure in dogs were investigated and following results were obtained. Colistin salts caused marked and sustained fall in blood pressure. Among them, C-S showed the most marked effect. C-M showed very week effect compared with the others. Marked tachyphylaxis was seen on the depressor effect by the repeated administration. Histamine-like substances in blood in dog by the administration of colistin salts were quantified. The quantity of them was the most when it produced maximum fall in blood pressure. The effect of colistin salts on the blood pressure in rabbits was the same as that of histamine.

Allergy as the etiology of chronic sinusitis

The author studied on influence of allergy upn chronic sinusitis. Using various antigen, 123 patients with chronic sinusitis were examined by skin tests. Mucous membrane of the maxillary sinus in 65 cases of these was surgically removed, of which the extract was made. After the extract was reacted in vitro on positive antigen when the skin tests were positive, and on house dust when they were negative, histamine-like substance and plasmin values were calculated. Histological investigation was made on all of the cases and compared with those values.The following results have been obtained.1. Skin tests were positive in 21 per cent of all the cases with chronic sinusitis. This rate was almost the same as normal one. Positive reaction of skin tests was due to inhalative antigen, which consists of house dust.2. Histamine-like substance values in mucous membrane in the maxillary sinus were unrelated with reaction of antigen.3. Comparison of values for reacted and non-reacted plasmin by antigen in mucous membrane was performed, and no significant difference was shown.4. There was no constant relation between histamine-like substance value reacted by antigen and change of plasmin value.5. Histamine-like substance and plasmin were produced after reaction by antigen from cases of positive skin tests and after reaction by house dust from cases of negative skin tests. Comparision of histamine-like substance and plasmin values afteraboth of reactions was shown no significant difference.6. There was no particular finding histologically in cases with positive skin tests, increased plasmin value and increased histamine-like substance value.As mentioned above, there was no proof that allergy plays an important role in the cause of chronic sinusitis.

Effect of Intraventricularly Injected Anticerebral Antibodies on the Histamine-like Substance and Potassium Content of Various Regions of the Brain of the Cat

IN an attempt to investigate the possible differential reactivity of various cerebral structures when exposed to the action of different brain region anti-sera, it has been shown that the injection of heterologous anti-caudate nucleus antibody into the lateral cerebral ventricle of the cat was followed by pronounced electrographic abnormalities, confined mainly to the caudate nucleus. Since the electrical activity of other, simultaneously investigated brain regions was not essentially modified, the alterations observed were interpreted as being strongly suggestive of the possibility that the anti-caudate antibody has an affinity for the homologous nervous tissue1.