Modulation of infection-induced inflammation and locomotive deficit and longevity in senescence-accelerated mice-prone (SAMP8) model by the oligomerized polyphenol Oligonol.

Oligonol is produced from the oligomerization of polyphenols (typically proanthocyanidin from a variety of fruits such as lychees, grapes, apples, persimmons, etc.) and contains catechin-type monomers and oligomers of proanthocyanidins. The ability of Oligonol to affect infection-dependent eye inflammation, locomotion and longevity in senescence-accelerated prone mice (SAMP8) (a model of senescence acceleration and geriatric disorders with increased oxidative stress and neuronal deficit) was investigated. Oligonol (60mg/kg) significantly modulated the extent of inflammation scores in the eye of SAMP8 mice. Examination of the mice indicated infection with mouse hepatitis virus and pinworm (Syphacia obvelata) in both males and females and with the intestinal protozoa (trichomonad) in males. A comparison of the two groups (using log-rank test) and the difference in the mean life span between groups (using Student's t-test) indicated significant differences in survival (p=0.043) and the mean life span (p=0.033) in male SAMP8 mice. Oligonol increased the mean life span and this was statistically significant. In the open-field locomotive test, the 7-week-old SAMP8 mice crossed more than 40 partitioned lines in 1min. At 48-week-old control untreated male SAMP8 crossed 2 lines. The Oligonol-treated 48-week-old male SAMP8 mice crossed 17 lines however. The improved locomotive activity was statistically significant even after 36weeks in the Oligonol-treated male SAMP8 but this was not the case throughout the time course of the study in the Oligonol-treated female SAMP8. Thus Oligonol treatment to SAMP8 mice modulated the severity of infection-dependent inflammation, prolonged life-span and significantly improved locomotive activity indicating potential benefit to aging-associated diseases such as Alzheimer's or Parkinson's diseases. This presents potential for further research to define infection-dependent inflammation associated with degenerative conditions and the molecular mechanism of dietary antioxidant protection.     

A Drosophila melanogaster hobo-white+ vector mediates low frequency gene transfer in D. virilis with full interspecific white+ complementation

Transformation of a Drosophila virilis white mutant host strain was attempted using a hobo vector containing the D. melanogaster mini-white⁺ cassette (H[w⁺, hawN]) and an unmodified or heat shock regulated hobo transposase helper. Two transformant lines were recovered with the unmodified helper (HFL1), one containing only the white⁺ marked vector, and a sibling line containing the vector as well as an HFL1 helper integration. An approximate total transformation frequency of 1% is deduced. A high frequency of wing and eye morphology mutants were also observed, suggesting that hobo may have mobilized a related element in D. virilis. The data reaffirms a relatively low transformation vector activity for the hobo transposon in D. virilis; however, nearly full interspecific expression of the white⁺ marker supports its possible function in other species as well.     

Immunoglobulin G4 antibodies to rat urinary allergens, sensitization and symptomatic allergy in laboratory animal workers

BACKGROUND AND OBJECTIVES: We have previously reported that high rat urinary allergen (RUA) exposure was not associated with increased risk of rat allergy in long-term-exposed laboratory animal (LA) workers. We aimed to assess whether strong allergen-specific IgG4 responses could explain the absence of a dose response in these subjects. We investigated whether IgG4 was associated with allergen exposure and prevalence of sensitization or respiratory symptoms to rats. The longitudinal relation between IgG4 and rat allergy was studied using data obtained during 2 years of follow-up. METHODS: Five hundred and twenty-nine LA workers answered a questionnaire on respiratory symptoms and occupational history and participated in skin prick testing. Blood samples were analysed for specific IgG4 and IgE to RUA. Exposure to RUA was estimated based on personal air samples. The relation between IgG4 and newly occurring sensitization or rat allergy was studied in workers who were not sensitized or did not report respiratory symptoms to rats. RESULTS: IgG4 titres were higher in atopic than in non-atopic subjects, and increased with higher allergen exposure. Titres were highest in subjects who were sensitized and reported respiratory symptoms to rats when compared with those who were not (geometric mean [geometric standard deviation] = 202 [5.7] vs. 8.4 [18.3] AU). The association between IgG4 and sensitization or symptomatic rat allergy was independent of estimated allergen exposure. IgG4 was a strong predictor of newly occurring sensitization and symptomatic rat allergy during follow-up in atopic and rat-sensitized subjects. CONCLUSION: High exposure to RUA is associated with a strong allergen-specific IgG4 antibody response. High anti-RUA IgG4 is a strong predictor of prevalent and incident sensitization and symptomatic rat allergy in atopic and rat-sensitized subjects. IgG4 can therefore not explain the absence of a dose response between allergen exposure and allergy in long-term-exposed workers. We consider anti-RUA IgG4 to be a marker that combines aspects of exposure and susceptibility.     

Chromatic pattern-reversal electroretinograms (ChPERGs) are spared in multiple system atrophy compared with Parkinson’s disease

Abstract Idiopathic Parkinson’s disease (IPD) patients have abnormal visual evoked potentials (VEPs) and pattern electroretinograms (PERGs), attributed to dopaminergic transmission deficiency in visual pathway, probably the retina. VEP abnormalities are not reported in multiple system atrophy (MSA). The aim of this study was to investigate and compare chromatic (Ch) red-green (R-G) and blue-yellow (B-Y), and luminance yellow-black (Y-Bk) PERGs in patients with MSA and IPD. We investigated 6 MSA patients (mean age: 62±7.4 years) not undergoing any pharmacological treatment, as well as 12 early IPD patients (mean age: 60.1±8.3 years) and 12 age-matched normal observers. ChPERGs were recorded monocularly in response to full-field equiluminant R-G, B-Y and Y-Bk horizontal gratings. In MSA only responses to R-G stimuli showed minimal insignificant changes (slight but not significant amplitude reduction without any significant latency delay); no significant abnormality was detected for B-Y and luminance Y-Bk stimuli. By contrast, in IPD all responses were reduced in amplitude and delayed in latency, above all for B-Y stimuli. Present data indicate that both chromatic and achromatic PERGs are virtually unaffected in MSA, whereas in early IPD they are clearly impaired, suggesting different pathogenic retinal mechanisms and a useful simple tool for distinguishing MSA from IPD.     

Amputation in elderly and high-risk vascular patients

Fifty-eight patients underwent lower limb amputation for arterial disease over a 30-month period. Mean age of the patients was 72 years. Cardiopulmonary and metabolic risk factors were present in the majority of the patients. Postoperative one-year and three-year mortality rates were 24, 40, and 76%, respectively. Contralateral amputation was required in one-third of the patients after a mean period of eight months. Only younger and healthier patients returned to a meaningful social life after appropriate prosthetic fitting. In view of the high mortality and morbidity rates, above-knee amputation seems a better choice than below-knee amputation in these elderly and high-risk patients.     

Validation of esophageal pressure occlusion test after paralysis

Measurements of respiratory mechanics are frequently made in ventilated infants and children. Esophageal pressure measurements (P_es using a balloon on a catheter have been used to partition the respiratory mechanics into lung and chest wall components. Appropriate positioning of this balloon is crucial to obtain accurate estimates of pleural pressure. Traditionally, in spontaneously breathing subjects the balloon position is assessed with an occlusion test. In ventilated subjects, it is not always possible to perform an occlusion test prior to paralysis, and even if such a test is performed it may not be relevant under conditions of positive pressure ventilation. We have assessed a positive pressure occlusion test that is suitable for paralyzed subjects. By occluding the airway opening and applying gentle pressure to the abdomen or rib cage, positive swings in pressure can be measured by both P_es and airway opening pressure (P_ao). We compared traditional occlusion tests measured in 16 spontaneously breathing puppies to the positive pressure occlusion test performed after paralysis. In 2 pups we were unable to obtain a reasonable traditional occlusion test (>15% difference between P_es and P_ao) but we obtained 10 traditional occlusion tests in each of the remaining 14 pups (2.1–14 kg). In 11 of these animals Ape, was within 10% of P_ao. This compared well to positive pressure occlusion test using abdominal pressure performed after paralysis, where Apes was within 10% of ΔP_ao in 10 animals. In 9 of these pups occlusion tests were also performed by applying pressure on the rib cage, where ΔP_es was within 10% of ΔP_ao in 6 animals. These results suggest that it is possible to perform accurate occlusion tests in paralyzed subjects by abdominal or rib cage compression with the airway occluded. Pediatr Pulmonol. 1994; 17:56–62. © 1994 Wiley-Liss, Inc.     

Neuro-ophthalmic manifestations of the syndrome of ophthalmoplegia, ataxia and areflexia Observations on 20 patients

The neuro-ophthalmological manifestations of 20 patients with the syndrome of ophthalmoplegia, ataxia and areflexia are described. The symmetrical nature of the ophthalmoplegia and the associated cerebellar ataxia point to centrally placed lesions. Several supranuclear, nuclear and internuclear ophthalmological signs are identified. Some of these, like partial sparing of the levator palpebrae and normal downgaze in the presence of severe ophthalmoplegia are noted too frequently to be just unusual signs of peripheral oculomotor dysfunction. Other identified features included upper lid retraction on attempted upgaze and preserved Bell's phenomenon in the presence of paralysis of the latter, as well as several other central ophthalmological signs. These findings contrast with those seen in the Guillain-Barré syndrome and, thus, the syndrome of ophthalmoplegia, ataxia and areflexia is not a mere variant of it.     

An electron microscopic study of local anesthetic-induced skeletal muscle fiber degeneration and regeneration in the monkey

An electron microscopic study was done on abductor pollicis brevis muscles of 18 Rhesus monkeys after intramuscular injections of 0.75% bupivacaine, 2% mepivacaine, or 2% lidocaine + epinephrine. The muscles were examined for from 2 h to 28 days. Severe muscle fiber damage, consisting of breakdown of sarcolemma and myofibrils, was seen as early as 2 h. Phagocyte mediated fragmentation of the degenerating muscle fibers was at its peak during the third and fourth days. Myoblasts were abundant during the fourth day. Early myotubes appeared on the fifth and sixth days, and they matured during the second week. Satellite cells appeared alongside mature myotubes. Overall, the local anesthetic-induced breakdown and regeneration of skeletal muscle fibers in the monkey followed a course quite similar to that seen in the rat.