Effect of vinpocetine on retrograde axoplasmic transport

Vinpocetine, a derivate of vincamine, is widely used in the clinical pharmacotherapy of cerebral circulatory diseases. Herewith we report on a novel effect of vinpocetine: inhibition of retrograde axoplasmic transport of nerve growth factor (NGF) in the peripheral nerve. Blockade of retrograde transport of NGF results in transganglionic degenerative atrophy (TDA) in the segmentally related ipsilateral superficial spinal dorsal horn, which is characterized by depletion of the marker enzymes fluoride-resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP). At the same time, pain-related neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), are depleted from lamina I-III from the segmentally related, ipsitateral Rolando substance of the spinal cord. On the basis of these experiments it is suggested that vinpocetine may result in a locally restricted decrease of nociception, that might be useful in clinical treatment of intractable pain. Pilot self-experiments support this assumption.     

Normally unused positional cues guide ectopic afferents in the leech CNS.

Central projections from peripheral sensory neurons segregate into distinct, ventrally positioned longitudinal tracts within the segmental ganglia of the leech Hirudo medicinalis. As documented here, there is an additional tract in the neuropils of the fifth and sixth body ganglia, located at the lateral margin and formed by afferent axons (the "sex afferents") originating from sensory neurons located in the male and female genitalia. Ablation of the genitalia results in the complete absence of this additional tract. We asked (1) whether segmental differences exist in the distribution of pathway cues available to the sex afferents, and (2) whether central pathway selection by these axons is specific. We transplanted the primordia of the male genitalia to several ectopic positions posterior to the sixth body segment and labeled the ectopic sex afferents in order to examine their paths in the CNS. In about 50% of the experimental animals, afferent axons originating in the transplanted tissue segregated into a distinct lateral fiber bundle within the neuropil of a nearby ganglion, in a position corresponding to their normal one in the sex ganglia. The sex afferents therefore find their normal pathways even in the ganglia of inappropriate segments, although these pathways are not used by any other afferents in these ganglia. We propose, therefore, that the positional cues employed by afferent axons to select appropriate pathways in the ganglionic neuropil are expressed in all segments of the leech CNS, regardless of whether such cues are normally used by afferent axons in each segment.     

Cardiac sensitization induced by phenobarbitone and prolonged by CS2

The arrhythmogenic effect of 8 g/kg noradrenaline given i.v. was increased in male rats pretreated 1–2 day s earlier with phenobarbitone and starved from the time of the first phenobarbitone injection (80 mg/kg followed by 50 mg/kg 6 h later). Daily exposure to 4.0 mg/l CS₂ (first exposure 24 h after the first phenobarbitone injection) for 4 h prevented the decline in susceptibility on the 3rd and 4th days after phenobarbitone, when the reaction of unexposed rats to noradrenaline returned to normal.     

Quinol-based metabolic cycle for estrogens in rat liver microsomes.

According to a recently reported metabolic pathway, phenolic A-ring estrogens are metabolized in rat liver microsomes partially to the corresponding quinols by cytochrome P450 isoenzymes. We found that these quinols could, in turn, undergo reduction to regenerate the parent estrogens consumed during the metabolic process. Among the tested endogenous reducing agents, NADH and especially NADPH produced a significant extent of reductive conversion. Enzymes available in rat liver microsomes further catalyzed this reaction with 6.5 +/- 1.5 nmol. min(-1). (mg of protein)(-1) measured as the initial rate of estrone formation at 37 degrees C, whereas the initial rate of second-order reaction for the reduction of E1-quinol by a 10-fold excess of NADPH in a microsome-free buffer solution and under identical incubation conditions was 0.62 +/- 0.03 nmol. min(-1). The quinol route is, therefore, unique among estrogen-metabolizing pathways for its bioreversibility due to the facile regeneration of the phenolic A-ring estrogens consumed in the preceding oxidative process.     

Large lung bullae in marijuana smokers

The case histories are presented of four men with multiple large upper zone lung bullae but otherwise relatively preserved lung parenchyma. Each had a history of significant exposure to marijuana. In three of the four cases the tobacco smoking load had been relatively small, suggesting a possible causal role for marijuana in the pathogenesis of this unusual pattern of bullous emphysema.     

Office Systems and Their Influence on Mammography Use in Rural and Urban Primary Care

CONTEXT: Breast cancer screening rates are lower in rural communities. Although studies have addressed barriers to mammography for rural residents, physician practice barriers have received less attention. PURPOSE: Controlled clinical trials have shown that the use of office reminder systems in primary care practices is related to increased clinical care rates. Therefore, we compared office systems use in primary care practices located in rural and urban communities and assessed the impact of these systems on rural-urban differences in mammography utilization. METHODS: We identified female Kansas Medicare beneficiaries aged 65 to 79 from Medicare claims data (N = 24,030) and determined which beneficiaries received a mammogram between April 1, 1999, and March 31, 2001. We linked beneficiaries to their primary care providers and obtained surveys from 180 primary care practices on their use of office reminder systems. FINDINGS: Mammography rates ranged from 20% to 92% (mean = 65%) among the 180 practices. Flowsheets with a mammography prompt were used by 33% of the practices, 38% utilized nonphysician staff to identify women due for mammograms, and 15% used computerized reminder systems. Urban practices used flowsheets more often than rural practices (44% versus 16%, P < 0.001). A multivariable regression model demonstrated higher mammography rates in urban practices, group practices, and practices using mammography flowsheets. CONCLUSIONS: Despite success in randomized controlled trials, reminder systems are not used often by primary care providers and are used even less often in rural compared to urban practices. Consistent implementation may be a major barrier to the successful adaptation of flowsheets by primary care offices.     

Primary cardiac sarcomas may develop from resident or bone marrow‐derived mesenchymal stem cells: use of immunohistochemistry including CD44 and octamer binding protein 3/4

Hegyi L, Thway K, Fisher C & Sheppard M N
(2012) Histopathology  61, 966–973 Primary cardiac sarcomas may develop from resident or bone marrow‐derived mesenchymal stem cells: use of immunohistochemistry including CD44 and octamer binding protein 3/4 Aims: To provide evidence that cardiac sarcomas ‘not otherwise specified’ express markers that might indicate their cellular origin or identify any lines of differentiation. Methods and results: We reviewed all 11 cases of primary undifferentiated cardiac sarcomas found in the archives of the Royal Marsden and Royal Brompton Hospitals, London, UK during the period 2000–2009. Five cases with appropriate consent and archived material were investigated using immunohistochemistry. We found that the spindle, pleomorphic or occasionally epithelioid cell sarcomas showed no lineage‐specific differentiation other than partial myofibroblastic or ‘myoid’ differentiation (all cases). All tumours showed some degree of cytoplasmic positivity for the mesenchymal stem cell marker CD44. In contrast, no nuclear octamer binding protein 3/4 (Oct3/4) expression was seen in any of the tumours, although very patchy cytoplasmic positivity was seen in some tumours. Conclusions: The cytoplasmic positivity for CD44 and the absence of nuclear Oct3/4 suggest that the cells of these sarcomas may represent ‘daughter’ stem cells that no longer have the capacity for tumour initiation, but have subsequently developed new lines of partial differentiation. Primary cardiac sarcomas may arise from mesenchymal stem cells with the ability to generate tumours with multilineage differentiation.