Metabolic disorder of otoconia after streptomycin intoxication

Little is known about the origin or the metabolism of otoconia. Streptomycin sulfate was found to cause a decrease in their number on the otolithic membrane of the utricle and saccule in guinea pigs. The remaining otoconia on the otolithic membrane varied in shape and size and giant otoconia with multilayered arrangement were observed by means of a scanning electron microscope. These otoconia contained the normal amount of calcium in the form of standard calcium calcite crystal. The lost otoconia were found attached to the surface of some vestibular dark cells. Otoconia in this new position were irregular, shrunken or fragmented. Their calcium content, measured with an X-ray micro-analyzer, was variably diminished. The dark cells appeared to be actively engaged in absorption of calcium ions, from the attached otoconia. The dark cell is considered to be a receptacle for the disposal of otoconia.     

Uptake of tetracycline in otoconia of the guinea pig

Calcium ion turnover in the otoconia of adult guinea pigs was investigated by observing the uptake of tetracycline. Oral administration of tetracycline resulted in the deposition of tetracycline (fluorescence) on the outer surface of otoconia, indicating the occurrence of dynamic exchange and/or uptake of calcium ions in the otoconia. Prolonged administration of tetracycline induced with fluorescence deposition in the central portion as well as on the surface of the otoconia. These findings suggest the occurrence of neogenesis, regeneration and/or growth of otoconia even in adult animals.     

Hungarian population data on the loci HLA-DQ alpha, LDLR, GYPA, HBGG, D7S8 and GC

45CaCO3 was injected into guinea pigs, and the radioactivity in otolithic membranes of utriculi and sacculi, auditory ossicles and femora was determined by liquid scintillation spectrometry, to study the dynamic effect of streptomycin on calcium content of otolithic membranes, as a means to explore the mechanism of streptomycin ototoxicity. The results showed that otoconium was a dynamic structure which took up 45Ca in a time course generally comparable to that of bone. Saccular otolithic membranes showed greater intake than utricular membranes. The calcium ion concentration of saccular endolymph was greater than that of the utriculus and the two maculas were not identical. Streptomycin may influence 45Ca uptake in the two macular otolithic membranes, causes calcium metabolic disorder and a fall of otolithic calcium content. It is possible that the fluid environments of the endolymph have changed, therefore dysfunction of otolithic organ may occur. This hypothesis may be one of the explanation of the mechanism of streptomycin ototoxicity.     

Trichlorethylene-, carbon tetrachloride- and gasoline-intoxication in connection with arterio- and coronary sclerosis (author's transl)

On the occasion of autopsies of 4 toxicomaniac adolescents sniffing and occasionally drinking trichlorethylene, carbon tetrachloride and gasoline severe arteriosclerotic damage of the coronary vessels was encountered. Experimental intoxication of 12 rabbits with these solvents over a period of 10 weeks, each time until a prenarcotic stage, provoked pathological changes in accordance with well known findings but no arteriosclerosis. Ergometrical examination with simultaneous recording of the E.C.G. of 6 adolescents with solvent-sniffing history and of 1 man, working for years under trichlorethylene exposure conditions and showing symptoms of chronic intoxication, revealed no signs of coronary-artery insufficiency. These findings are not inconsistent with the assumption -- though not substantiating it -- of a causal relationship between the intoxication with trichlorethylene, carbon terachloride and gasoline and the development of arteriosclerosis, as the coronary sclerosis may be of the elstic type with a very high degree of adaptability and the probands proved unable to reach the limit of maximum stress. In addition to the main purpose the occurrence of epileptic seizures following chronic trichlorethylene sniffing in one case and the manifestation of pulmonary obstruction following i.v. application of Methyl-Phenidat (Ritalin) in two cases are reported.     

Lead and the kidney: nephropathy, hypertension, and gout

Lead intoxication in human beings has been documented since the second century B.C. Renal disease, hypertension, and gout have all been linked to lead by strong circumstantial evidence. Both acute and chronic nephropathy can occur as a result of lead poisoning. Acute renal failure develops following acute lead intoxication and is often associated with gastrointestinal, neurologic, and hematologic disorders. Both blood and urinary laboratory abnormalities are associated with acute intoxication and are often diagnostic. Chronic lead nephropathy, a chronic tubulointerstitial nephritis on biopsy, occurs in the setting of long-term lead exposure and is often associated with hypertension and gout. Diagnosis of chronic lead nephropathy is more difficult since the laboratory abnormalities seen with acute lead intoxication are not present with chronic lead exposure. The typical clinical picture and the exclusion of other causes of renal disease allow the diagnosis of chronic lead nephropathy to be made. Evaluation of lead stores by either the calcium disodium edetate (EDTA) mobilization test or K-x-ray fluorescence are helpful in clinching the diagnosis. Treatment with EDTA lead mobilization is effective for acute lead poisoning while avoidance of further lead exposure prevents recurrence of lead intoxication. Treatment of chronic lead nephropathy with EDTA lead mobilization is useful if renal failure is modest; however, EDTA mobilization is of no benefit in patients with more severe renal insufficiency.     

Laryngeal survey in glyphosate intoxication: a pathophysiological investigation

Respiratory aspiration is a serious potential complication of glyphosate-surfactant herbicide intoxication. From October 1, 1992 to June 30, 1996, we performed laryngeal evaluations in 53 cases to investigate the possible pathophysiological mechanism of glyphosate intoxication. There were 36 cases with significant laryngeal injury. The blood WBC count were significantly higher and the hospital stays were significantly longer in patients with laryngeal injury, when compared with patients with no laryngeal injury (Student t-test, P < 0.005). Laryngeal injury was strongly correlated with aspiration pneumonitis (mean 2 = 4.449, P < 0.05). We concluded that laryngeal injury may be the major cause of aspiration that leads to some degree of morbidity and mortality, following concentrated glyphosate-surfactant herbicide intoxication. Laryngeal survey may be indicated in cases of glyphosate-surfactant intoxication, to evaluate the severity of mucosal injury, and to apply adequate supportive management as early as possible to prevent from aspiration complications and even mortality.     

Tissue response to nano-hydroxyapatite/collagen composite implants in marrow cavity

The formation of otoconia in the endolymphatic sac (ES) of the larval newt, Cynops pyrrhogaster, has been studied by light and transmission electron microscopy. Some of the epithelial cells of the ES contain an abundance of swollen vesicles, Golgi complexes, rough endoplasmic reticula and ribosomes at the late larval stages 50 and 51, approximately 26-30 days after eggs are laid. Five days later, at stage 52, crystals are present in the vacuoles between the epithelial cells. Serial sections indicate that these vacuoles actually form small canals which lie in the wall and join the lumen of the ES. Reconstruction of the ES shows that several canals are contained in the ES wall. At stage 56, about 72 days after eggs are laid, a large number of otoconia are present in the ES lumen, while the otoconia disappear from the canals. It appears that the otoconia are first produced in the canals and then released to the lumen. Some epithelial cells of the ES are thought to expel the organic and inorganic material to the canals to form the otoconia in situ. The process of formation of the otoconia in the ES is discussed.     

Toxicity and side effects of antibiotics in radiation sickness and during the use of aminothiol group radioprotective agents

It was shown in experiments on mice, rats and rabbits that resistance of animals in the state of acute radiation sickness to severe intoxication by aminoglycoside antibiotics, such as streptomycin, dihydrostreptomycin and monomycin did not significantly change. The exception was kanamycin the toxicity of which during the period of the acute state of radiation sickness increased by 30 per cent. The use of cystamine and merkamine before irradiation or their administration to non-irradiated animals resulted in lowering of the antibiotic tolerance by 1.5--2 times. The above aftereffects of the radioprotectors was observed within 3--12 days after their use and was most pronounced for the combination of cystamine and streptomycin. The acute toxicity of tetracyclines did not significantly differ at various stages of radiation disease and at the background of cystamine use. No significant cumulation of the toxicity of aminoglycoside antibiotics and tetracyclines or signs of adaptation in the healthy and irradiated animals was observed on prolong treatment with therapeutic doses. Cystamine had no effect on the tolerance of the antibiotics on their prolonged use.     

A study of mortality and urinary excretion of oxalate in male rats following acute experimental intoxication with diethylene-glycol. Preliminary report

Acute intoxication by diethylene glycol (LD 50) in male rats is associated with a considerable urinary excretion of oxalate, which is significantly decreased by alkalinisatin and/or intraperitoneal injection of ethanol with hydration. Mortality during the five days following intoxication is significantly decreased by major hydration only or together with pyridoxine administration, but is cancelled by major hydration together with alkalinisation or intraperitoneal administration of ethanol, plus hydration, with or without alkalinisation. -- It might be inferred that diethylene glycol has the same metabolic pathway as ethylene glycol and treatment of acute intoxication by diethylene-glycol should be the same as that of acute poisoning with ethylene glycol.     

An electrophysiological study of the postnatal development of the corticospinal system in the macaque monkey

We characterized toxin-insensitive calcium currents expressed by acutely dissociated embryonic dorsal root ganglion neurons. In the presence of 3 microM omega-conotoxin-GVIA, 3 microM nitrendipine and either 500 nM omega-agatoxin-IVA or 500 nM omega-conotoxin-MVIIC to inhibit N-, L- and P/Q-type currents, respectively, all neurons expressed two residual currents: a T-type and another which we referred to as toxin-resistant current. The toxin-resistant current (i) consisted of an inactivating and a sustained components, (ii) had a threshold of activation and a steady-state inactivation comprised between that of the T-type current and that of the other high-voltage-activated currents, (iii) had the same permeability for barium and calcium used as charge carriers, (iv) was highly sensitive to both cadmium and nickel; and (v) was insensitive to 500 microM amiloride which abolished the T-type at this concentration. The properties of the toxin-resistant current are very similar to those of the currents expressed in oocytes following injection of alpha(1E) subunits which we demonstrated to be present in these neurons. Therefore a component of the toxin-resistant current calcium channels in sensory neurons may be closely related to those calcium channels formed by alpha(1E) subunits.     

Nonrestricted differential intoxication of cells by pertussis toxin

After uptake and retrograde transport pertussis toxin acts by ADP-ribosylating alpha-Gi proteins. We show that uptake via many different receptor proteins followed by retrograde transport and intoxication is not restricted to a particular cell type. The efficiency of cellular intoxication, however, was found to be cell type dependent.     

Clinical evaluation of a prototype motion artifact resistant pulse oximeter in the recovery room

Isolated posterior semicircular canals (psc) of bull frogs were used for a model of positional vertigo. Induced ampullary nerve action potentials were recorded. When the cupula was removed and the saccular otoconia were dropped onto the cilia, excitatory, and inhibitory potentials were evoked by changing the psc positions into canal-down and canal-up, respectively. When the otoconia were allowed to stay on the cupular surface, canal-down and canal-up positions also evoked excitatory and inhibitory responses, respectively. When the otoconia were inserted in the canal and were allowed to move, changing the psc positions likewise evoked responses. However, when one end of the canal was closed, these responses disappeared, indicating the efficacy of canal plugging.     

Acute effects of morphine on regional brain levels of acetylcholine in mice and rats

Electrophoretic injection of Procion Yellow M-R4 into the ocellar tract of the worker bee has revealed the following: Two types of giant axon run from the lateral ocellus to the circumesophageal neuropile, where one branches ipsilaterally and the other contralaterally. A third type comes from the median ocellus and can be traced into the cervical connectives. The largest dendritic complex is in the circumesophageal neuropile; in addition, fiber endings have been demonstrated in the following areas: in the subretinal region, along the optic commissure, in the medulla interna, in the subesophageal ganglion and between the neurosecretory cells of the pars intercerebralis. -- The giant fibers are enclosed in a glial sheath. Three types of cell body are described. One is associated with the glia; another, larger cell type comprises giant-axon somata. The third type of cell is small, and cannot yet be identified. Some of the histological results are discussed with respect to the possible function of the ocellus.     

The Ranvier nodes in the neurogenic electric organ of the knifefish Sternarchus: a freeze-etching study on the distribution of membrane-associated particles

The two types of Ranvier nodes (type I with narrow gap, type II with giant gap) and internodes in nerve fibers composing the Sternarchus electric organ have been studied by means of freeze-etching electron microscopy. Numerical analysis of the distribution of membrane-associated particles revealed the following features: (1) the P-faces of both types of nodes and of the internodal axon bear a similarly high density of particles (1000-1200 particles/sq. micron on the average). (2) particle density is differential in E-faces: the histogram for type I nodes has a wider range of particle concentrations (114-1522 particles/sq. micron) than that for type II nodes (45-576 particles/sq. micron) whose density values are in the same range as those of the internodal axon. At least some type I nodes (narrow gaps) generate spikes and probably have a low resistivity; these nodes may be those with high particle density on E-faces. The low particle density on E-faces of type II nodes may be associated with high resistivity and absence of excitability. Similarly, the low particle density in internodes may reflect inexcitability. There is evidence that the transition from one nodal type to the next is gradual: as the gap width of type I nodes increases, there is an occurrence of surface elaborations and the density of E-face particles tends to drop towards the range of type II nodes.     

Effect of the prolonged use of streptomycin as well as streptomycin in combination with tubazid on the bioelectrical activity of the brain in experimental tuberculosis]

The effect of streptomycin used alone and in combination with tubazid on the brain electric activity was studied in chronic experiments on rabbits with tuberculosis. The electrocorticographical investigations showed that the antibacterial treatment lowered the spontaneous electric activity and reactive capacity of the cortex. It was evident from a narrow amplitude of the main rythm, coefficient and energy of synchronization on rythmic photostimulation and paroxysmal activity withing the theta range. With the account of the high therapeutic effect of the antibacterial treatment evident from minimum affection of the organs with tuberculosis, the above changes in the electrocorticogrammes should be attributed to the neurotropic effect of the drug and not to tuberculosis intoxication.     

Observations on the different calcium metabolic patterns in sarcoidosis. A metabolic and kinetic study

Combined calcium balance and 47Ca turnover studies in sarcoidosis (4 patients) and vitamin D intoxication (1 patient) disclosed three different patterns of calcium metabolism. On patient with sarcoidosis had a normal metabolism of calcium, and two patients presented the usual pattern of intestinal hyperabsorption, hypercalcemia, and hypercalciuria. The fourth patient with sarcoidosis and the patient with vitamin D intoxication, both studied during spontaneous remissions, presented the third pattern. The main features here were hypercalcemia despite normal intestinal absorption of calcium, enlarged exchangeable calcium pool, accelerated accretion and resorption rates, hypercalciuria, and a distinctly negative calcium balance. This pattern of remission seems to represent a mobilization of extraosseous or metastatic calcifications, rather than a resorption of bone calcium.     

Odontogenic focus as the etiology of cerebral ischemia]

Several authors have established a relationship between osteoporosis and periodontal disease. The ageing process is associated with a loss of both oral and total bone mass. It has been shown that a reduction of bone mineralization aggravates pathological periodontal changes, resulting in less support for the teeth. The present study investigates the nutritional influences that may condition the appearance of both pathological process. Insufficient dietary calcium and a reduction in the calcium: phosphorous ratio may favour the appearance of both these conditions by promoting bone reabsorption. Bone loss affects the following in descending order: jaw bones (especially alveolar bone), cranial bones, ribs, vertebrae and long bones. Alveolar bone which has the highest rate of renewal, is affected first and consequently is the most severely affected in the long term. The role of calcium in the etiology of osteoporosis is a controversial issue. Nevertheless, its implication has been proven in numerous investigations. The effect of adequate calcium intake on dental health has formed the basis of several recent studies. These investigations have demonstrated that increased calcium intake improves the suffering of inflammatory processes and tooth mobility in patients suffering from gingivitis with haemorrhaging. Based on the results of studies which link dietary calcium and phosphorous to the risk of osteoporosis and periodontal disease, and bearing in mind that in a large proportion of the Spanish population calcium intake is below that recommended, there is a need for a general improvement of the diet. It may be of special interest to increase the calcium intake of patients suffering periodontal disease. It may also help in the prevention of osteoporosis.     

Transrectal prostate puncture biopsy in ambulatory care

One may not rely solely on serum lithium levels to detect or prevent lithium intoxication. A review of the reported cases of serious lithium intoxication despite "therapeutic" blood levels of lithium is presented, along with a discussion of possible explanations for the phenomenon. Possible alternate means of following a patient on lithium carbonate are discussed.     

Dietary vitamin A intake in relation to child growth

Protective effects of calcium antagonists, chlorpromazine (CPZ) and nimodepine (NI-MO), on cadmium-induced toxicity were investigated. After giving CdCl2 (0.44 mg Cd/kg, i.p.), CPZ (5 mg/kg, i.p.) or NIMO (8 mg/kg, p.o.) were administered every day to Sprague-Dawley (S.D.) rats for a week. Then, urinary N-acetyl-beta-D-glucosaminidase (NAG), urinary cadmium and blood cadmium were measured. The accumulation of cadmium in the kidney cortex, content of renal calmodulin, hemoglobin and the ultrastructural damage of proximal convoluted tubules of rats were examined three weeks after the last administration. Results indicated that the calcium antagonists partly protected against toxic effects induced by cadmium in different manners. These data provide further evidence for the new hypothesis that the cross effect of cadmium and calcium in calmodulin regulated systems may be responsible for the mechanism of cadmium intoxication. The results suggested that the calcium antagonists could be a new and promising approach in the therapy of heavy metal-induced diseases.     

Commentary: Esophageal carcinoma confined to the wall--the need for immediate definitive therapy

Twenty-six Holstein calves with clinical and pathological effects suggesting a toxic plant intoxication were studied. A view of the plants in the region and blood examination (hemogram, albumin, total protein, calcium and phosphorus) and determination of bone calcium were done. Five calves were slaughtered and pathological examinations were performed. Observed metabolic, pathological and clinical alterations were compatible with intoxication from Cestrum diurnum.