Developmental Neurotoxicity Evaluation of Orally Administered Isopropanol in Rats

Isopropanol was administered by gavage to timed-mated rats fromGestation Day (GD) 6 through Postnatal Day (PND) 21. Doses administeredwere 0, 200, 700, or 1200 mg/kg/day in a volume of 5 ml/kg.The dams were allowed to deliver and body weights and food consumptionwere recorded during gestation and lactation. Pups were counted,examined, sexed, and weighed on PND 0, 4, 7, 13, 17, 21, 36,49, and 68. Litters were culled to eight pups (4:4 or 5:3 sexratio) on PND 4 and litters without acceptable numbers of maleand female pups were eliminated from the study. Pups were weanedon PND 22, and two pups from each litter and their dams werekilled. Six of these pups from each dose group were perfusedin Situ for histopatho logical examination of the central andperipheral nervous sys tem. Brains of the remaining pups weredivided into four regions and weighed. Maternal liver and kidneyweights were re corded. Weaned pups were assessed for day oftestes descent or vaginal opening and for motor activity onPNDs 13, 17, 21, 47, and 58; auditory startle on PNDs 22 and60; and active avoidance on PNDs 60–64. These pups wereeuthanized and examined on PND 68. One high-dose dam died onPND 15, but there were no other clinical observations or effectson maternal weight, food consumption, or gestation length. Pupsurvival, weight, sex ratio, and sexual maturation were unaffected.There were no biologically significant findings in the behavioraltests, no changes in organ weights, and no pathological findingsthat could be attributed to isopropanol exposure. In conclusion,there was no evidence of developmental neurotoxicity associatedwith isopropanol exposure as high as 1200 mg/kg/day.     

Disposition and Pharmacokinetics of Isopropanol in F-344 Rats and B6C3F1 Mice

The absorption, metabolism, disposition, and excretion of isopropanol(IPA) were studied in male and female rats and mice. Animalswere exposed by iv (300 mg/kg) and inhalation (500 and 5000ppm for 6 hr) routes; additionally, IPA was given by gavageto rats only in single and multiple 300 and 3000 mg/ kg doses.In the rat approximately 81–89% of the administered dosewas exhaled (as acetone, CO₂, and unmetabolized IPA); approximately76% of the dose in mice was exhaled after iv bolus but 92% wasexhaled following inhalation. Approximately 3–8% of theadministered dose was excreted in urine as IPA, acetone, anda metabolite tentatively identified as isopropyl glucuronicacid. Small amounts of radiolabel were found in feces and inthe carcass. There were no major differences in the rates orroutes of excretion observed either between sexes or betweenroutes of administration. Additionally, repeated exposure hadno effect on excretion. However, both the route of administrationand the exposure or dose level influenced the form in whichmaterial was exhaled. Following exposure to 5000 ppm, a greaterpercentage of unmetabolized IPA was recovered in the expiredair than following exposure to 500 ppm, implying saturationof metabolism.     

Carcinogenic Potential of Gasoline and Diesel Engine Oils

Used gasoline engine oils are carcinogenic in mouse skin andmutagenic in Salmonella. The toxicity of fresh gasoline engineoils and that of fresh and used diesel engine oils are lesswell defined. The present studies examined the dermal carcinogenicpotential of a series of fresh and used oils from both gasolineand diesel engines. The used oils represented a variety of operatingconditions. The objective of the study was to assess the potentialcarcinogenic hazards associated with exposure to these materials.The majority of the used gasoline engine oils tested were carcinogenicalthough one oil, collected after a relatively short drainageinterval, was inactive in the dermal carcinogenesis bioassay.Additionally, polycyclic aromatic hydrocarbon (PAH) concentrationswere elevated in the used oils in comparison to the fresh oils.The fresh gasoline engine oils and both the fresh and used dieselengine oil samples were noncarcinogenic, and there was littleevidence of elevated PAH levels in the used diesel engine oils.The carcinogenic potency of used oils from gasoline engineswas related to drainage interval, but other factors such ascontribution of the fuel due to blowby and driving cycle mayalso have been important. The used diesel engine oils were notcarcinogenic even after extended use.     

Infantile myofibromatosis: a light microscopic, histochemical and immunohistochemical study suggesting true smooth muscle differentiation

Eight cases of infantile myofibromatosis, a rare, sometimes multicentric neoplasm which shows an inherited tendency, have been studied by light microscopy, conventional histochemistry and immunohistochemistry. This tumour is commonest in early infancy and may arise at a wide variety of sites, most often in subcutaneous tissue. Evidence is presented that this entity shows true smooth muscle differentiation, rather than it being of a myofibroblastic nature and hence its current name may be incorrect. In this context, the presence of desmin positivity in six out of eight cases is of particular importance. The differential diagnosis is discussed.     

Activity,friendships and wellbeing in residential settings for older people

Friendships have been demonstrated to influence an individual's psychological wellbeing.This paper reports an investigation into whether friendships influence the psychological wellbeing of residents in long-stay care settings for older people. The study consisted of the observational assessment of activity in 64 residents drawn from three care settings, together with brief structured interviews assessing self-reports of friendships and psychological wellbeing. Results indicated that non-intimate friendships were more common than close friendships. Activity levels were higher in residents with good friends compared to residents without good friends, but the degree of difference was dependent on the home in which the resident lived. Neither activity levels nor friendships were associated with residents' wellbeing. Qualitative analysis of fieldnotes indicated that the pattern of friendships found in the residential settings was influenced by resident choice, the prevailing care regime and aspects of the physical environment. Results are discussed in relation to disengagement theory, the importance of reminiscence in later life, and methodological issues in the measurement of wellbeing in older people.     

Our Postpandemic World: What Will It Take to Build a Better Future for People and Planet?

Policy Points

• Despite the pandemic''s ongoing devastating impacts, it also offers the opportunity and lessons for building a better, fairer, and sustainable world.
• Transformational change will require new ways of working, challenging powerful individuals and industries who worsened the crisis, will act to exploit it for personal gain, and will work to ensure that the future aligns with their interests.
• A flourishing world needs strong and equitable structures and systems, including strengthened democratic, research, and educational institutions, supported by ideas and discourses that are free of opaque and conflicted influence and that challenge the status quo and inequitable distribution of power.

     

Cellular schwannoma: a distinct pseudosarcomatous entity

Eighteen cases of cellular schwannoma, a recently delineated benign entity, are described. These tumours present most often in middle-aged adults of either sex and show a predilection for the paravertebral region of the mediastinum and retroperitoneum. More than half the tumours macroscopically arose from a nerve but none was associated with von Recklinghausen's disease. The light microscopic features are remarkably consistent but are not immediately recognizable as neural in type. Means of distinction from a malignant nerve sheath tumour and from a variety of other soft tissue tumours are discussed. Immunohistochemical positivity for S-100 protein has been demonstrated in 17 of the 18 cases. Prolonged follow-up has revealed local recurrence in only one case; none has metastasized.     

Retroperitoneal Fibrosis Caused by Carcinoid Tumor

This report describes a 33-year-old woman who presented withrenovascular hypertension secondary to retroperitoneal fibrosis,associated with a carcinoid tumor with widespread metastases.Although the association is rare, it is important to considercarcinoid tumour as a cause of idiopathic retroperitoneal fibrosis,even in the absence of the carcinoid syndrome.