High HIV incidence in men who have sex with men attending for postexposure prophylaxis: a service evaluation.

BACKGROUND/AIMS: There are limited outcome data for men who have sex with men (MSM) who have received HIV postexposure prophylaxis (PEP). The objective of this service evaluation was to determine HIV incidence and repeat PEP use among MSM PEP recipients in London, UK. METHODS: Retrospective electronic case-note review of all MSM who were prescribed PEP between January and April 2013 at a central London sexual health service. RESULTS: 530 MSM received PEP between 1 January and 30 June 2013. Of these, 449 had more than 30 days subsequent follow-up at our service. Median age was 31 years. PEP indication was unprotected anal intercourse, 98% (receptive 88% and insertive 10%) and other, 2%. Up to 1 November 2015, total follow-up was 756 person-years. 183 users received repeat PEP. The total number of repeat PEP courses was 442. 57 MSM newly acquired HIV: the HIV incidence was 7.6 per 100 person-years. CONCLUSIONS: PEP was associated with a high risk of subsequent HIV seroconversion in this cohort; this group may be appropriate candidates for pre-exposure prophylaxis.

Propolis as an autophagy modulator in relation to its roles in redox balance and inflammation regulation.

Autophagy is a degradation process that is evolutionarily conserved and is essential in maintaining cellular and physiological homeostasis through lysosomal removal and elimination of damaged peptides, proteins and cellular organelles. The dysregulation of autophagy is implicated in various diseases and disorders, including cancers, infection-related, and metabolic syndrome-related diseases. Propolis has been demonstrated in various studies including many human clinical trials to have antimicrobial, antioxidant, anti-inflammatory, immune-modulator, neuro-protective, and anti-cancer. Nevertheless, the autophagy modulation properties of propolis have not been extensively studied and explored. The role of propolis and its bioactive compounds in modulating cellular autophagy is possibly due to their dual role in redox balance and inflammation. The present review attempts to discuss the activities of propolis as an autophagy modulator in biological models in relation to various diseases/disorders which has implications in the development of propolis-based nutraceuticals, functional foods, and complementary therapies.

Characterisation of triterpenes and new phenolic lipids in Cameroonian propolis.

Chemical investigation of a sample of propolis originating from North-Western Cameroon led to the isolation of thirteen alk(en)ylphenols (1-13) (inseparable mixture) along with α-amyrin (14), ß-amyrin (15), lupeol (16), cycloartenol (17), mangiferonic acid (18), ambonic acid (19), mangiferolic acid (20), ambolic acid (21), isomangiferolic acid (22) and nine alk(en)ylresorcinols (23-31) (inseparable mixture). All compounds were identified following analysis of their spectroscopic data and comparison with previously published reports. Compounds (8), (12), (13) and (30) are new natural products. GC-MS analysis carried out on the alk(en)ylphenol and alk(en)ylresorcinol mixtures (dimethyl disulphide trimethylsilyl derivatives) revealed the presence of saturated and mono-unsaturated compounds with side chain lengths ranging from C11 to C19 and C15 to C19, respectively. The position of the double bond in mono-unsaturated derivatives was established from the characteristic fragments resulting from the cleavage of the bond between the two methylthio-substituted carbons. The most abundant compound in each mixture was 3-(12'Z-heptadecenyl)-phenol (10) and 5-(12'Z-heptadecenyl)-resorcinol (29). This study is the first to report the presence of triterpenes (except for lupeol) and phenolic lipids, including eighteen compounds previously unreported in bee glue, in an African sample.

Application of principal components analysis to 1H-NMR data obtained from propolis samples of different geographical origin.

Propolis is a widely used natural remedy and a range of biological activities have been attributed to it. The chemical composition of propolis is highly variable and its quality is often controlled on the basis of one or two marker compounds. In order to progress towards a method for the quality control of this complex material, HPLC and 1H-NMR approaches as methods of quality control have been compared. HPLC analyses of 43 samples of propolis were carried out and six marker compounds were quantified in each sample. The same samples were analysed using 1H-NMR and the spectra were then converted into their first derivative forms and digitised using the software application MestRe-C. The digitised data were subjected to principal component analysis using the software application Simca-P. It was found that the chemical composition of propolis mapped well according to the geographical origins of the samples studied when the first three principal components were used to display them. In addition, each sample was assessed for anti-oxidant activity, and the results were then overlaid onto the sample groupings according to 1H-NMR data. It was observed that anti-oxidant properties also mapped quite well according to geographical origin.

Striatonigral degeneration. A clinicopathological study.

The clinical and pathological features of 10 cases of striatonigral degeneration are described: 5 were misdiagnosed in life as Parkinson's disease. Retrospectively, helpful early pointers to the diagnosis in these cases included unexplained falls, autonomic dysfunction, absence of rest tremor and failure to respond to L-dopa, but these were not always present. The pathological diagnosis could not be excluded on macroscopic examination of the striatum. Relative preservation of the putamen occurred in the 4 patients who benefited from L-dopa. The caudate nucleus was involved in all cases and there was no sparing of the large striatal neurons. In mild cases, involvement of the putamen was confined to its posterior two-thirds, dorsolaterally. With increasing severity this extended in a dorsal to ventral and posterior to anterior direction. Seven of the cases had evidence of olivopontocerebellar damage, but only 2 of these had clinical evidence of cerebellar disease. Correlation was found between the neuronal counts in caudate:putamen, striatum:nigra compacta, globus pallidus:nigra compacta, nigra compacta:locus coeruleus. The most severely involved part of the substantia nigra pars compacta was the ventrolateral zone, which projects to the dorsal putamen, the earliest site of striatal disease.

Ageing and Parkinson's disease: substantia nigra regional selectivity.

The micro-architecture of the substantia nigra was studied in control cases of varying age and patients with parkinsonism. A single 7 mu section stained with haematoxylin and eosin was examined at a specific level within the caudal nigra using strict criteria. The pars compacta was divided into a ventral and a dorsal tier, and each tier was further subdivided into 3 regions. In 36 control cases there was a linear fallout of pigmented neurons with advancing age in the pars compacta of the caudal substantia nigra at a rate of 4.7% per decade. Regionally, the lateral ventral tier was relatively spared (2.1% loss per decade) compared with the medial ventral tier (5.4%) and the dorsal tier (6.9%). In 20 Parkinson's disease (PD) cases of varying disease duration there was an exponential loss of pigmented neurons with a 45% loss in the first decade. Regionally, the pattern was opposite to ageing. Loss was greatest in the lateral ventral tier (average loss 91%) followed by the medial ventral tier (71%) and the dorsal tier (56%). The presymptomatic phase of PD from the onset of neuronal loss was estimated to be about 5 yrs. This phase is represented by incidental Lewy body cases: individuals who die without clinical signs of PD or dementia, but who are found to have Lewy bodies at post-mortem. In 7 cases cell loss was confined to the lateral ventral tier (average loss 52%) congruent with the lateral ventral selectivity of symptomatic PD. It was calculated that at the onset of symptoms there was a 68% cell loss in the lateral ventral tier and a 48% loss in the caudal nigra as a whole. The regional selectivity of PD is relatively specific. In 15 cases of striatonigral degeneration the distribution of cell loss was similar, but the loss in the dorsal tier was greater than PD by 21%. In 14 cases of Steele-Richardson-Olszewski syndrome (SRO) there was no predilection for the lateral ventral tier, but a tendency to involve the medial nigra and spare the lateral. These findings suggest that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of PD.

Superficial siderosis of the central nervous system.

There have been 87 cases of superficial siderosis of the CNS reported in the world literature and 63 cases had developed the clinical syndrome with sufficient details to be reviewed. It is a distinct clinical syndrome characterized by sensorineural deafness (95%), cerebellar ataxia (88%) and pyramidal signs (76%). Other features include dementia (24%), bladder disturbance (24%), anosmia (at least 17%), aniscoria (at least 10%) and sensory signs (13%). Less frequent features are extra-ocular motor palsies, neck or backache, bilateral sciatica and lower motor neuron signs (5-10% each). Males are more often affected than females (3:1). The age of onset ranged from 14 to 77 years, age at death from 29 to 78 years and duration until death from 1 to 38 years excluding premature death due to the underlying cause or as a result of surgery. Up to 27% become bed bound at 1-37 years from the first symptom due to either cerebellar ataxia, a myelopathic syndrome or both. Symptomatic subarachnoid haemorrhage occurred in 37% and the CSF was haemorrhagic and/or xanthochromic in 75%. It is now accepted that superficial siderosis is due to chronic subarachnoid haemorrhage and a source of bleeding has been reported in 54% of cases; it was either due to dural pathology (47%) including a CSF cavity lesion or cervical root lesion, a vascular tumour (35%) or a vascular abnormality (18%). Arguments are presented that the remaining cases were also due to chronic haemorrhage and that there is no evidence for a non-haemorrhagic form of superficial siderosis. There have been 14 incidental cases diagnosed by MRI or at post-mortem with no symptoms attributable to superficial siderosis during life, supporting the notion of a pre-symptomatic phase to the illness. In 22 patients who had developed the syndrome, the duration of this pre-symptomatic phase could be calculated and ranged from 4 months to 30 years with an average of 15 years. At present the most promising treatment for superficial siderosis is surgical ablation of the bleeding sources.

Diffuse Lewy body disease presenting with a supranuclear gaze palsy.

A patient with diffuse Lewy body disease presented with supranuclear vertical and horizontal ophthalmoplegia, dementia, axial rigidity and falls, bradykinesia and pyramidal signs. This broadens the clinical presentation of this pathological diagnosis and re-emphasises the heterogeneity of patients diagnosed clinically as progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome).

Comet assay and flow cytometry analysis of DNA repair in normal and cancer cells treated with known mutagens with different mechanisms of action.

In order to determine differences in repair after treatment with DNA damaging agents, normal and cancer cells were selected for analysis of single strand breaks and DNA crosslinks using the Comet assay. Normal human lymphocytes, human colorectal adenocarcinoma SW620 cells, lung carcinoma A549, and H460 cell lines were exposed to an ethylating agent (ethylmethane sulfonate [EMS]), and a cross-linking agent (mitomycin C [MMC]). Differences in repair profiles of DNA damage demonstrated using the comet assay were observed in human lymphocytes and tumour cell lines with both mutagens. Results were also indicative that MMC repair is concentration-dependent. It was also apparent that normal cells repair DNA damage more readily than tumour cells. Repair also varied between different cell lines. To investigate the mechanistic differences of these two chemicals, flow cytometry studies were undertaken in tumour cells, namely cell cycle analysis and frequency of micronuclei induction (FMN). A G2M phase block was clearly evident following treatment with EMS at all concentrations tested. With MMC, an initial arrest of cells in G2M was accompanied by a build-up in S-phase over longer exposure periods. Also, at the highest mutagen doses there were different patterns of micronuclei induction. Thus, using the mutagens with different mechanisms of action highlighted the differences in repair patterns between normal and tumour cells.

Neurological illness following treatment with fludarabine.

Fludarabine is a comparatively new drug for the treatment of low-grade lymphoid malignancy. This report describes five cases of unusual neurological illnesses occurring after treatment with fludarabine. These suggest that caution should be exercised in patients receiving fludarabine who develop neurological abnormalities, with prompt investigation and if necessary cessation of the drug.