Penetration and distribution of three lipophilic probes in vitro in human skin focusing on the hair follicle.

Fluorescent model substances of increasing lipophilicity (Oregon Green) 488, Bodipy, FL C5 and Bodipy 564/570 C5) were selected to enable the visualization in the skin using confocal laser scanning microscopy. After measuring the penetration for 18 h, the nonfixed human scalp skin was imaged from the bottom parallel to the stratum corneum and in a cross-section view perpendicular to the skin surface. The images were evaluated by calculating relative accumulation values for different penetrants. The studies indicate that the penetrated amount is highest for Bodipy FL C5 (medium lipophilicity) and lowest for Bodipy 564/570 C5 (high lipophilicity) whereas Bodipy 564/570 C5 (high lipophilicity) reveals the highest relative accumulation in parts of the hair follicle compared to Oregon Green 488 (low lipophilicity). The addition of 30% (v/v) ethanol to the donor phase of substance with a low lipophilicity increases the follicular delivery. From our results we conclude that delivery to the hair follicle can be improved by increasing the drugs lipophilicity and optimizing the composition of the donor phase. However, no conclusion can be drawn about the actual route of transport to the hair follicle.     

Molecular cloning of agonistic and antagonistic monoclonal antibodies against human 4-1BB.

Previously, we prepared two different monoclonal antibodies (mAbs) against human 4-1BB (CD137): an agonistic mAb BBK-1 and an antagonistic mAb BBK-2. In this paper, we describe the molecular cloning of these two mAbs and present comparisons of their amino acid sequences. cDNAs encoding the heavy (H) and light (L) chains of the two mAbs were cloned by screening of cDNA libraries constructed from hybridomas secreting these mAbs. Comparisons of amino acid sequences of the two mAbs showed that, while the constant regions of the H and L chains were identical between the two mAbs, the variable region showed 45% identity in H chains and 48% identity in L chains. This suggests that these two mAbs recognize different epitopes of 4-1BB and may have different effects on the activity of 4-1BB.     

Delivery of therapeutic doses of doxorubicin to the mouse lung using lung-accumulating liposomes proves unsuccessful

Cancer Chemotherapy and Pharmacology - Addition of solid doxorubicin or solutions to pre-formed liposomes proved to be the optimal method for incorporating the drug into liposomes whilst...     

The contribution of reoxygenation to ischemic brain damage

This study examined the hypothesis that the level of postischemic reperfusion affects the severity of the resulting neuronal necrosis. In rats, tissue PO2% was monitored as an index of flow (reoxygenation) at four cortical sites by chronically implanted platinum electrodes. Twenty minutes of total global cerebral ischemia was followed by 30 min of reoxygenation. The level of reoxygenation was controlled to maintain the PO2 nearly constant at one or more of the cortical electrodes. Tissue from within 400 microns of each of 19 electrode sites among seven rats was evaluated histologically. There was a positive correlation between reoxygenation level and severity of neuronal damage. Perineuronal lucent halo formation, probably representing astrocyte foot process swelling, was negatively correlated with reoxygenation level. This study demonstrates that ischemic neuronal damage was aggravated by increased reoxygenation but that perineuronal swelling, as evidenced by halo formation, was somewhat ameliorated.     

Humoral and cellular immunity following severe head injury: review and current investigations.

Infection is a common and serious complication of severe head injury. Immunocompetence in 25 severely head injured patients was investigated by measuring: (1) delayed-type hypersensitivity (DTH) skin test responses to common antigens; (2) phytohaemagglutinin (PHA) stimulated peripheral blood lymphocyte (PBL): blastogenesis, phenotype expression, and lymphokine production; (3) lymphokine-activated killer (LAK) cytotoxicity, antibody dependent cellular cytotoxicity (ADCC) and natural killer (NK) cytotoxicity; and (4) immunoglobulin and complement levels. The incidence of anergy to DTH skin testing was 100%. There was a decrease in PHA stimulated: PBL blastogenesis (p = 0.002), T-cell expression (p = 0.018), helper T-cell expression (p less than 0.001), interleukin-2 receptor expression (p less than 0.001), interleukin-2 production (p = 0.035) and gamma-interferon production (p less than 0.001). LAK cytotoxicity was depressed following incubation with IL-2 (p less than 0.001). There was no significant decrease in immunoglobulin levels and all acute phase reactants tested increased. The results of this study indicate that the cellular arm of immune response, including lymphocyte activation and cytokine production, is suppressed following severe head injury. The lack of enhancement in LAK cytotoxicity following incubation of PBLs with interleukin-2 suggests that factors other than decreased interleukin-2 production, such as the inherent lymphocyte dysfunction, other soluble mediators or suppressor cells, may be responsible for the reduction in cellular immunity observed following severe head injury.     

Babinski-Nageotte syndrome on magnetic resonance imaging

A 70-year-old woman developed left hypoglossal nerve palsy, a right hemiparesis sparing the face, and a typical left Wallenberg's syndrome. These symptoms resulted from a lesion in the left half of the medulla oblongata, suggesting Babinski-Nageotte syndrome, a rare cerebrovascular disease. This is the first case of ischemic infarction in the territory of the left vertebral artery and posterior inferior cerebellar artery demonstrated on magnetic resonance imaging. Severe bilateral lesions of the distal vertebral arteries demonstrated on digital subtraction angiography may have contributed to the development of this syndrome.     

Lithium treatment of chronic hair pulling

Ten patients with chronic hair pulling received trials of lithium carbonate of 2 to 14 months' duration. Eight patients demonstrated decreased hair pulling and mild to marked hair regrowth. Three responders experienced increased hair pulling subsequent to discontinuation of lithium treatment. Lithium's effect on hair pulling may be related to its observed benefits in treating aggressivity, impulsivity, and mood instability.