Effects of consumption of contaminated feed with 2,4-dichlorophenoxyacetic acid (2,4-D) on the rat tibia: analysis by Raman spectroscopy and mechanical properties

Lasers in Medical Science - Studies reported the harmful effects of 2,4-D on body tissues, provoking changes in the anatomy and physiology of the kidneys, liver, and testicles. Thus, the objective...     

Novel Compounds Identified by Structure-Based Prion Disease Drug Discovery Using In Silico Screening Delay the Progression of an Illness in Prion-Infected Mice

The accumulation of abnormal prion protein (PrP^Sc) produced by the structure conversion of PrP (PrP^C) in the brain induces prion disease. Although the conversion process of the protein is still not fully elucidated, it has been known that the intramolecular chemical bridging in the most fragile pocket of PrP, known as the “hot spot,” stabilizes the structure of PrP^C and inhibits the conversion process. Using our original structure-based drug discovery algorithm, we identified the low molecular weight compounds that predicted binding to the hot spot. NPR-130 and NPR-162 strongly bound to recombinant PrP in vitro, and fragment molecular orbital (FMO) analysis indicated that the high affinity of those candidates to the PrP is largely dependent on nonpolar interactions, such as van der Waals interactions. Those NPRs showed not only significant reduction of the PrP^Sc levels but also remarkable decrease of the number of aggresomes in persistently prion-infected cells. Intriguingly, treatment with those candidate compounds significantly prolonged the survival period of prion-infected mice and suppressed prion disease-specific pathological damage, such as vacuole degeneration, PrP^Sc accumulation, microgliosis, and astrogliosis in the brain, suggesting their possible clinical use. Our results indicate that in silico drug discovery using NUDE/DEGIMA may be widely useful to identify candidate compounds that effectively stabilize the protein.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00903-9) contains supplementary material, which is available to authorized users.     

Somatosensory and spinal evoked potentials in patients with cervical syringomyelia.

We recorded somatosensory evoked potentials (SEPs) from the skin surface and spinal evoked potentials (SpEP) from the posterior epidural space after median nerve stimulation in 11 patients with cervical syringomyelia. We compared SEPs with SpEP to assess the possible feasibility of using these techniques to localize the offending lesion. SEP abnormalities were present on one or both sides of 7 patients (9 of 22 upper limbs; 41%). The abnormal SEP pattern was the attenuation or loss of N13, which was of little value for delineating the lesion. In patients with abnormal SEPs, three types of abnormal SpEPs were noted. In the Type A abnormality (three limbs), potentials were attenuated in all cervical segments, suggesting that the syrinx itself had enlarged to involve the posterior column. In Type B (two limbs), there was reduced amplitude or absent upper cervical potentials, probably a result of the accompanying tonsilar herniation. Finally, the Type C (four limbs) abnormality was a mixture of Type A and B abnormalities in that the attenuated cervical potentials were again affected in the most upper cervical segment. We concluded that SpEP revealed various kinds of involvement of the dorsal column pathway in the syringomyelic patients, a finding not expressed with conventional SEPs.     

Familial pituitary adenoma--report of four cases from two unrelated families.

The authors report four cases of familial pituitary adenomas from two unrelated families. No clinical or biochemical evidence of multiple endocrine neoplasia, type I (MEN-I) was demonstrated. Detailed study of the family trees disclosed no other family members affected by MEN-I. Familial occurrence of pituitary adenomas unassociated with MEN-I is rare.     

Evaluation of telephone transmission for computer electrocardiographic interpretation in Japan

The reliability of the Japanese public telephone facilities to transmit electrocardiograms (e.c.g.) for computer interpretation was assessed. The International Business Machine's (IBM) e.c.g. computer program by Bonner was used. No appreciable distortion of e.c.g. was observed following repeated transmission from hospitals separated by 1000 km. Thirty-four normal and 66 abnormal e.c.g.s. were transmitted twice. Identical results were observed in 97% of normals and 92% of abnormals. Following these fundamental experiments, 1236 patients' e.c.g.s. were transmitted for computer intepretation. The study showed that 98·6% (1219 cases) were technically satisfactory and 1·4% (17 cases) were not. The 17 unsatisfactory cases were classified into ten unreceivable data formats, six inconsistent measurements and one unacceptable noise level. The authors concluded that the Japanese public telephone facilities were acceptable for the transmission of e.c.g.s. for computer interpretation.     

Incidence and characterization of age related amyloid deposits in the human anterior pituitary gland

Summary To identify amyloid deposits in the anterior pituitary gland, we have immunohistochemical, histochemical and alkaline Congo red staining. The anti-human P component reacted positively with these amyloid deposits, while antisera against prealbumin, AA type amyloid fibril protein and various anterior pituitary hormones were negative. A combination of Congo red and anti-human P component staining was most sensitive and reliable for detection of amyloid in the anterior pituitary glands of 300 randomly autopsied patients. Amyloid deposits increased in parallel with the age of the patients, however, they appeared earlier and more frequently than heretofore reported. Deposition of amyloid was seen initially in the 3rd decade and the positivity rate of amyloid deposits was 73% in the 5th decade. The histochemical characteristics of these pituitary amyloid deposits differed from those of cerebral and systemic deposits, particularly those found in the amyloid of senile systemic amyloidosis.This study was supported in part by a grant from the Fundation for Advancement of Clinical Medicine and Ministry of Health and Welfare of Japan     

Changes in element concentrations induced by agonist in pig pancreatic acinar cells

 Changes in electrolytes of pig pancreatic acinar cells following application of gastrin-cholecystokinin (CCK) were investigated using the technique of X-ray microanalysis of hydrated and dehydrated sections of freshly frozen pancreas. After stimulation by CCK (10^–9 M), Na and Cl increased significantly in the cytoplasm [Na, from 10 mmol/kg wet wt. (48 mmol/kg dry wt.) to 19 mmol/kg (95 mmol/kg); Cl, from 22 mmol/kg (105 mmol/kg) to 49 mmol/kg (245 mmol/kg)] as well as in the luminal interspace [Na, from 53 mmol/kg (189 mmol/kg) to 65 mmol/kg (283 mmol/kg); Cl, from 65 mmol/kg (232 mmol/kg) to 102 mmol/kg (443 mmol/kg)]. In the secretory granules Cl increased significantly from 30 mmol/kg (86 mmol/kg) to 67 mmol/kg (203 mmol/kg). K decreased significantly from 120 mmol/kg (571 mmol/kg) to 81 mmol/kg (405 mmol/kg) in the cytoplasm, while both increased from 38 mmol/kg (109 mmol/kg) to 58 mmol/kg (176 mmol/kg) in the granules and from 46 mmol/kg (164 mmol/kg) to 48 mmol/kg (209 mmol/kg) in the luminal interspace. Ca increased significantly in the cytoplasm as well as in the luminal interspace, and decreased significantly in the secretory granules. CCK evoked Ca release from secretory granules in the secretory pole of acinar cells. The values were measured from dehydrated sections, and agreed well with those from hydrated sections. The effect of furosemide, an inhibitor of the Na⁺-K⁺-2Cl^–co-transporter, on the ion transport of acinar cell was studied. When furosemide (10^–5 M) was added to the external solution, the cytoplasmic Cl and Ca concentrations decreased significantly, while there was a little decrease in Na and K concentrations under the secretory condition. These results indicate that Na⁺-K⁺-2Cl^–co-transport, and Na⁺, Cl^–and K⁺ exits into the lumen are involved in the mechanism of ion secretion in pig pancreatic acinar cells. Received: 17 January 1996 / Accepted: 12 March 1996