Recalcitrant hypertrophic herpes genitalis in HIV‐infected patient successfully treated with topical imiquimod

Herpes Simplex Virus type 2 is the primary cause of genital ulceration worldwide. The presence of atypical features like deep ulcerations, hypertrophic, or pseudotumoural lesions or unusual location can be a marker for co‐infection with HIV. These immunocompromised patients are usually resistant to the conventional antiviral treatment. We present a case of an HIV‐infected patient with hypertrophic herpes genitalis, refractory to conventional oral antiviral therapy, who was successfully treated with a combination of oral valcyclovir and topical application of 5% imiquimod.     

Corpus callosum size, reaction time speed and variability in mild cognitive disorders and in a normative sample

Intra-individual variability in reaction time increases with age and with neurological disorders, but the neural correlates of this increased variability remain uncertain. We hypothesized that both faster mean reaction time (RT) and less intra-individual RT variability would be associated with larger corpus callosum (CC) size in older adults, and that these associations would be stronger in adults with mild cognitive disorders. A normative sample (n=432) and a sample with mild cognitive disorders (n=57) were compared on CC area, RT mean and RT variability adjusting for age, sex, education, APOE genotype, smoking, alcohol consumption, grip strength, visual acuity, handedness and lung function. Samples did not differ in CC area or intra-cranial volume. In the normative sample, simple RT (SRT) and choice RT (CRT) were negatively associated with CC area but there were minimal associations between CC area and intra-individual RT variability. In the mild cognitive disorders sample, SRT, CRT and intra-individual variability on the SRT task were associated with CC area. Increased RT variability explained up to 12.7 percent of the variance in CC area in the sample with mild cognitive disorders, but less than 1 percent of the variance in CC area in the normative sample. There were no associations with APOE genotype. We conclude that intra-individual variability is associated with CC area in mild cognitive disorders, but not in normal aging. We propose that biological limits on reserve capacity must occur in mild cognitive disorders that result in stronger brain-behavior relationships being observed.     

Study of central gray nmda receptors in nociceptive behaviour in rats

1. 1. Cannulae were implanted stereotaxically in the PAG area in rats.

2. 2. Nociceptive thresholds were assessed in these rats, by measuring the tail flick latencies after post - operative recovery.

3. 3. Micro-injections of NMDA, L — aspartic acid and L — glutamic acid were made in the central gray and the effects on tail flick latencies studied.

4. 4. Low dose of NMDA in the PAG did not significantly alter the tail flick latencies, higher doses produced hyperalgesia.

5. 5. L — glutamic acid, aspartic acid, and Mk 801 induced hyperalgesia in the doses used. Ketamine did not significantly affect the tail flick latencies.

     

Pregnancy-induced obsessive compulsive disorder: a case report

Pregnancy is a well-recognised risk factor in precipitating obsessive-compulsive disorder. We present and discuss a case with the onset of obsessive-compulsive disorder in the fourth month of gestation, which fully recovered two weeks after delivery. The phenomenology of the observed disorder was similar to earlier reports of obsessive-compulsive disorder in pregnancy, i.e. the obsessions and compulsions were predominantly related to the concern of contaminating the foetus resulting in washing compulsions. Despite the initial success with anti-obsessional drugs, the patient stopped the medication in the last month of gestation. Nevertheless, she fully recovered two weeks after the delivery without any psychiatric intervention. There were no obsessive-compulsive symptoms at one-year follow up. The possible mechanisms involved in the aetiology of this case, and future research directions in understanding the role of pregnancy in OCD are discussed.     

In Vitro and In Vivo Antiviral Activity and Resistance Profile of the Hepatitis C Virus NS3/4A Protease Inhibitor ABT-450

The development of direct-acting antiviral agents is a promising therapeutic advance in the treatment of hepatitis C virus (HCV) infection. However, rapid emergence of drug resistance can limit efficacy and lead to cross-resistance among members of the same drug class. ABT-450 is an efficacious inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, and 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, and 6a, respectively. In vitro, the most common amino acid variants selected by ABT-450 in genotype 1 were located in NS3 at positions 155, 156, and 168, with the D168Y variant conferring the highest level of resistance to ABT-450 in both genotype 1a and 1b replicons (219- and 337-fold, respectively). In a 3-day monotherapy study with HCV genotype 1-infected patients, ABT-450 was coadministered with ritonavir, a cytochrome P450 3A4 inhibitor shown previously to markedly increase peak, trough, and overall drug exposures of ABT-450. A mean maximum HCV RNA decline of 4.02 log₁₀ was observed at the end of the 3-day dosing period across all doses. The most common variants selected in these patients were R155K and D168V in genotype 1a and D168V in genotype 1b. However, selection of resistant variants was significantly reduced at the highest ABT-450 dose compared to lower doses. These findings were informative for the subsequent evaluation of ABT-450 in combination with additional drug classes in clinical trials in HCV-infected patients. (Study M11-602 is registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01074008","term_id":"NCT01074008"}}NCT01074008.)     

Synthesis of Diene‐Functionalized Macromonomers via Functionalization with Hexa‐1,3,5‐triene

The reaction of poly(styryl)lithium (PSLi) with hexa‐1,3,5‐triene (HXT) was studied as a route to diene‐functionalized macromonomers. When PSLi was reacted with 1.5 molar equivalents of HXT for 2.5 h at ?10 °C in toluene, it was found that the diene‐functionalized macromonomer was obtained in high yield; however, oligomerization of the HXT was observed by matrix‐assisted laser absorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS). Oligomerization was eliminated by running the reaction with only 1.2 molar equivalents of HXT to PSLi and allowing the reaction to run for 15 min at ?10 °C in toluene. The resulting polymer exhibited high diene chain‐end functionality and no oligomerization was observed by MALDI‐TOF MS. ¹³C NMR spectroscopy and the attached‐proton test (APT), along with calculated chemical shifts, showed the presence of both the 1,2‐ and 1,4‐addition chain‐end structures. Further analysis by the reaction of the functional polymer with maleic anhydride indicated that 18 wt.‐% of the product was unreactive, either because of a 1,4‐addition chain‐end structure or a nonfunctional polymer. The structure of the maleic anhydride‐modified polymer was determined by MALDI‐TOF MS and ¹³C NMR spectroscopy. Preliminary work on the reactivity of the diene‐functionalized macromonomers was performed by the addition of a large excess of PSLi to a solution of macromonomer followed by characterization by size‐exclusion chromatography (SEC).

The formation of hexa‐1,3,5‐triene‐functionalized polystyrenes and their reaction with maleic anhydride.