Effect of defective collagen synthesis on epithelial implant interface: lathyritic model in dogs. An experimental preliminary study.

Peri-implant mucosa is composed of 2 compartments: a marginal junctional epithelium and a zone of connective tissue attachment. Both structures consist mainly of collagen. Lathyrism is characterized by defective collagen synthesis due to inhibition of lysyl oxidase, an enzyme that is essential for interfibrillar collagen cross-linking. The lathyritic agent beta-aminoproprionitrile (ß-APN) is considered a suitable agent to disrupt the connective tissue metabolism. Therefore, the purpose of this study was to assess the effect of defective connective tissue metabolism on epithelial implant interface by using ß-APN created chronic lathyrism in the canine model. Two 1-year-old male dogs were included in this study. A ß-APN dosage of 5 mg/0.4 mL/volume 100 g/body weight was given to the test dog for 10 months, until lathyritic symptoms developed. After this, the mandibular premolar teeth (p2, p3, p4) of both dogs were atraumatically extracted, and the investigators waited 3 months before implants were placed. In the test dog, 3 implants were placed in the left mandible, and 2 implants were placed in the right mandible. In the control dog, 2 implants were placed in the left mandibular premolar site. The dogs were sacrificed 10 months after healing. Peri-implant tissues obtained from the dogs were examined histomorphologically and histopathologically. Bone to implant contact (BIC) values and bone volumes (BV) were lower in the lathyritic group compared to the control group; however, no statistical significance was found. Significant histologic and histomorphometric changes were observed in peri-implant bone, connective tissue, and peri-implant mucosal width between test and control implants. Defective collagen metabolism such as lathyrism may negatively influence the interface between implant and surrounding soft tissue attachment.

The ratio 1660/1690 cm(-1) measured by infrared microspectroscopy is not specific of enzymatic collagen cross-links in bone tissue.

In postmenopausal osteoporosis, an impairment in enzymatic cross-links (ECL) occurs, leading in part to a decline in bone biomechanical properties. Biochemical methods by high performance liquid chromatography (HPLC) are currently used to measure ECL. Another method has been proposed, by Fourier Transform InfraRed Imaging (FTIRI), to measure a mature PYD/immature DHLNL cross-links ratio, using the 1660/1690 cm(-1) area ratio in the amide I band. However, in bone, the amide I band composition is complex (collagens, non-collagenous proteins, water vibrations) and the 1660/1690 cm(-1) by FTIRI has never been directly correlated with the PYD/DHLNL by HPLC. A study design using lathyritic rats, characterized by a decrease in the formation of ECL due to the inhibition of lysyl oxidase, was used in order to determine the evolution of 1660/1690 cm(-1) by FTIR Microspectroscopy in bone tissue and compare to the ECL quantified by HPLC. The actual amount of ECL was quantified by HPLC on cortical bone from control and lathyritic rats. The lathyritic group exhibited a decrease of 78% of pyridinoline content compared to the control group. The 1660/1690 cm(-1) area ratio was increased within center bone compared to inner bone, and this was also correlated with an increase in both mineral maturity and mineralization index. However, no difference in the 1660/1690 cm(-1) ratio was found between control and lathyritic rats. Those results were confirmed by principal component analysis performed on multispectral infrared images. In bovine bone, in which PYD was physically destructed by UV-photolysis, the PYD/DHLNL (measured by HPLC) was strongly decreased, whereas the 1660/1690 cm(-1) was unmodified. In conclusion, the 1660/1690 cm(-1) is not related to the PYD/DHLNL ratio, but increased with age of bone mineral, suggesting that a modification of this ratio could be mainly due to a modification of the collagen secondary structure related to the mineralization process.

The effect of lathyrism on dentin structure of the rat incisors: a morphometric and scanning electron microscopic investigation.

BACKGROUND: The present study was designed to study the effect of beta-aminopropionitrile (beta-APN), present in Lathyrus sativus grass pea consumed in drought prone areas, on dentin of the continuously erupting rat incisors. METHODS: Eighteen adult male rats were used. In the experimental group (18 rats), lathyrism was induced by a once daily subcutaneous administration of beta-APN for 40 days. The maxillary and mandibular incisors were examined ultrastructurally and morphometrically. RESULTS: The mean number of patent tubules, the mean area, perimeter and the area percent of the tubules were analyzed. Ultrastructurally, the dentinal tubules of both coronal and radicular dentin in the lathyritic group were narrower or even obliterated compared with those in the control. The coronal and radicular dentin of the lathyritic group exhibited an irregular lattice of non-mineralized small branching collagen fibrils obliterating the dentinal tubules. The mean number of patent tubules in the control and lathyritic groups revealed an insignificant difference. The mean area of the tubules showed a statistically significant difference in lathyritic radicular dentin (P = 0.0353). The percentage of the total surface area of the dentinal tubules significantly decreased in the radicular dentin of the lathyritic group (P = 0.024). CONCLUSIONS: These findings indicated a deleterious effect of lathyrism on dentin, with a possible negative impact on developing teeth integrity.

[Describing neurolathyrism. Physicians and the lathyrism epidemic in post-civil war Spain]. / Describiendo el neurolatirismo. Los clinicos ante la epidemia de latirismo en la Espana de la posguerra.

INTRODUCTION: Lathyrism is a chronic disease involving spastic paralysis of the lower limbs caused by the prolonged consumption of large amounts of flour made from grass pea, or almorta as it is known in Spain. In Spain it became an epidemic in the early post-civil war years, and this gave rise to a series of studies and clinical descriptions of unquestionable medical and historical interest. DEVELOPMENT: This paper analyses the clinical reports of patients with lathyrism during the above-mentioned epidemic in order to stress the importance of the symptoms and the neurological examination in identifying new cases and in controlling them. One interesting feature that stands out is how uniform these descriptions are, except in the initial phase of the disease, where certain differences have been reported depending on the epidemic area. Likewise, the (typical and atypical) prodromal symptoms, the classic symptoms of the disease and the so-called residual symptoms are all described. CONCLUSIONS: The lathyrism epidemic that occurred in Spain in the years 1941-1943 resulted in a series of clinical descriptions with very detailed accounts of the signs and symptoms written by the Spanish physicians who treated those patients. These reports constitute a valuable historical and clinical contribution on the subject of a disease that has been eradicated in west but is still endemic in other parts of the world.

Reduced reciprocal inhibition is seen only in spastic limbs in patients with neurolathyrism.

If reduced reciprocal inhibition plays a causal role in the pathophysiology of spasticity as has been suggested in several studies, the inhibition is expected to be impaired in spastic, but not in normal muscles. Patients with neurolathyrism offer a possibility of testing this prediction since the spastic symptoms in these patients are restricted to the lower extremities only. Three patients with neurolathyrism were tested. Their data were compared with 15 age-matched healthy subjects. All patients showed signs of spasticity in the legs. Two patients had normal voluntary muscle force in the lower extremities and one had decreased force. No clinical abnormalities were found in the upper extremities. Reciprocal inhibition between ankle dorsiflexor and plantarflexor muscles was absent in all patients, whereas the inhibition between wrist extensor and flexor muscles was present and of normal size and latency. These findings are consistent with the hypothesis that reduced reciprocal inhibition plays a causal role in the pathophysiology of spasticity.

Estudios sobre la escoliosis idiopática / Studies on idiopathic scoliosis

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Knowledge and management of disabling conditions in South Asian histories: implications for leprosy futures.

Elimination of leprosy as a public health problem appears feasible in South Asia in the present decade through multi-drug therapy, but management of disability in cured leprosy patients will continue through the 21st century, probably with some ongoing stigma. This paper provides new perspectives on leprosy-related disabilities by reviewing the historical careers of four disabling conditions sharing some features with leprosy: lathyrism, iodine deficiency disorders (IDD), cataract and poliomyelitis. All are targeted for eradication or serious reduction using affordable surgery or preventive measures, yet they have proved unexpectedly resilient. Technical solutions alone bring only partial success. There is a need also for community-based delivery methods, individual and family self-help, and some redeployment of professional expertise.

H reflex studies in neurolathyrism.

Sixteen patients with lathyrism, age ranging between 18 and 55 years and duration of illness between 2 and 25 years, underwent H reflex studies with the aim of studying motor neurone excitability. The patients had marked spasticity (Ashworth score ranging between 2 and 5) and mild to moderate leg weakness. Knee and ankle reflexes were exaggerated in all and the plantar response was extensor in 14 patients. The H reflex abnormalities included increased HM ratio indicating increased motoneurone excitability, significant lack of vibratory inhibition indicating altered transmission in the premotoneuronal portion of the H reflex pathway, and lack of reciprocal inhibition (P < 0.01). These H reflex abnormalities were not related to spasticity, weakness, clonus or plantar response. The H reflex recovery curve in 6 patients revealed increased excitability throughout the recovery curve. The secondary facilitation started and peaked slightly earlier than normal, and the late depression was not marked indicating change in excitability of motoneurones or of interneurones.

New findings and symptomatic treatment for neurolathyrism, a motor neuron disease occurring in north west Bangladesh.

Neurolathyrism is a form of spastic paraparesis caused by the neuroexcitatory amino acid 3-N-oxalyl-L-2,3-diaminopropanoic acid (beta-ODAP) present in the seeds and foliage of Lathyrus sativus. The disease is irreversible and usually nonprogressive. Tolperisone HCl, a centrally acting muscle relaxant, has been shown to reduce significantly the spasticity in neurolathyrism patients. Sporadic occurrence of HTLV-1 infection (0.9%) and of osteolathyrism was found among the neurolathyrism patients. Osteolathyrism is linked to the consumption of the green shoots of Lathyrus sativus.

Studies of the etiology and pathogenesis of motor neuron diseases. III. Magnetic cortical stimulation in patients with lathyrism.

Neurophysiological assessments of central motor pathways were conducted of 11 Spanish subjects with varying degrees of spastic paraparesis (lathyrism). The disease has been induced more than 40 years ago by subsistance on the neurotixic chick pea Lathyrus sativus. Patient evolution was carried out by magnetic cortical and electric spinal stimulations and recordings of the contralateral muscle responses. Central motor conduction times corresponding to lower limbs were clearly more prolonged in those severely affected patients with marked difficulty walking (Stages 4 and 3). Central conduction times corresponding to upper limbs were delayed in only 1 patient. Taken together with clinical and published neuropathological data, these findings suggest that established lathyrism is essentially a central motor system disorder primarily affecting corticospinal tracts regulating the lower limbs.

Studies on neurolathyrism.

Neurolathyrism is a neurological condition seen among people who eat the seeds of Lathyrus sativus (LS) as a principal source of food energy for 2 months or more. It is characterized by severe muscular rigidity and paralysis of the lower limbs. beta-N-Oxalyl-L-alpha,beta-diaminopropionic acid is the principal toxin found in the seed. No experimental animal model for neurolathyrism could be produced by feeding either the seeds or the toxin, although the condition has been known for centuries. We discovered that experimental neurolathyrism could be produced in guinea pigs and primates that needed an external supply of ascorbic acid by making them subclinically deficient in ascorbic acid and feeding them the seeds of LS or extracts thereof. Autoclaving the seeds of LS with lime removes the toxin.

Prevalence of paralytic poliomyelitis in rural and urban populations in Ethiopia: report of a house-to-house survey.

A house-to-house survey was carried out to determine the prevalence of poliomyelitis. During the survey 37,219 households were visited and 17,941 children 5-9 years old were found. Of 231 lame children, lameness compatible with paralytic poliomyelitis was found in 131, of these 91% had their condition before the age of 3 years. Nineteen percent needed a stick support for walking while 12% were unable to walk even with support. This problem was more common in rural populations. The prevalence of paralytic poliomyelitis was 7.3/1,000 children 5-9 years old.

Experimental lathyrism: exostoses and aneurysmal-like bone cysts of the mandible in the rat.

The effect of chronic lathyrism on the mandible of the rat was studied. Exostoses, thinning and discoloration of the cortical plates, intraosseous bleeding and hemorrhagic cyst were observed after six weeks of administration of beta-aminoproprionitrile fumarate. The exostoses consisted of homogeneous cellular fibrous tissue containing osteoid, hyalin-like material and abundant ground substance. The cysts were filled with erythrocytes and lined by spindle-shaped fibroblasts, collagen fibers or osteoblast-like cells. Between the cysts, bands and sheets of dense and cellular connective tissue presenting foci of hemorrhage, osteoid and metaplastic cartilage were found. Numerous mast cells were demonstrated with alcian and toluidine blue in the hematopoietic bone marrow, cancellous bone and around the capillary network surrounding the exostoses and cysts. Exostoses have already been studied and explained by the action of BAPN (lysyl oxidase). Hemorrhagic cysts could be explained by histamine release from the mast cells (hypervascularity, hyperemia, increased permeability, rupture and progressive confluence of these small hemorrhagic cysts). Histopathology of the experimental cysts had some points in common with the human aneurysmal bone cyst. Could the pathogenic mechanisms be similar for both lesions?

Postlathyric fibroelastosis of the rat aorta related to topical factors of experimental atherosclerosis.

Postlathyric aortic fibroelastosis was produced in rats with the aid of low-percentage fetal lathyrism. Subsequently the rats were kept on an atherogenic regimen for one year, and at the end of that period the aortas were studied to detect the relation of postlathyric alterations to the experimental atherosclerotic lesions. In the ascending aorta and the arch the fibroelastosis neither enhanced nor suppressed the development of mixed atherosclerotic plaques. In contrast, fibroelastosis of the thoracic and abdominal aorta usually causing a slight tunnel-shaped stenosis of the affected segment significantly reduced the development of intimal lipoidosis. The present experiment permitted to identify a new postlathyric lesion, namely sac-shaped microaneurysms situated at the sites of origin of lumbar arteries. Despite the fact that otherwise virtually the only lesion developing in the abdominal aorta was intimal lipoidosis, the aneurysms were filled up with mixed atheromatous masses. The above postlathyric vascular lesion appeared to significantly support the local development of atherosclerosis. The results presented have been discussed in view of the some recent facts stressing the indisputable importance of haemodynamic factors for the localization and development of atherosclerosis.

The experimental study of scoliosis in bipedal rat in lathyrism.

Using Wister albino rats, bipedal rats were prepared; to which semicarbazide at a concentration of 0.075%, 0.05% and 0.025% were given as drinking water and the rats were divided into three groups A, B and C according to such concentrations. Osteolathyrism was caused in this way and the relations between doses as well as the dosing period and the progress of scoliosis were examined roentgenologically and histologically and the following conclusions were obtained. 1. The frequency of occurrence of scoliosis was 82% in the bipedal rats and 13% in the quadrupedal rats (level of significance alpha = 0.001% or less). 2. Primordial top vertebrae were located concentratively in the lower 1/3 of thoracic vertebra. 3. In the primordial curve, those cases showing a right side curve accounted for 76%. 4. After termination of administration of semicarbazide, spontaneous improvement took place only in those cases showing scoliosis of less than 40 degrees. 5. In the author's experimental scoliosis, the static and dynamic condition of posture nearly coincided with those of men in clinical studies. 6. Histological changes were especially marked in the cartilage layer on the vertebral epiphyseal line, being quite diversified.

Experimental intracranial aneurysms in rats. A gross and microscopic study.

Experimental cerebral aneurysms were induced in rats in which the left carotid artery was ligated. The rats were rendered hypertensive by the Goldblatt procedure, and fed a diet containing beta-aminopropionitrile. These intracranial aneurysms have significant gross and microscopic similarities to human berry aneurysms. The procedures and microscopic observations indicate that this experimental model could be useful for studying the development, pathophysiology, and therapy of saccular aneurysms.