Purpose
Drug distribution in scalp hair can provide historical information about drug use, such as the date and frequency of drug ingestion. We previously developed micro-segmental hair analysis, ...which visualizes drug distribution at 0.4-mm intervals in individual hairs. The present study examines whether the distribution profiles of drugs can be markers for the administration or external contamination of the drugs using scalp, axillary, and pubic hairs.
Methods
A single dose of anti-itch ointment containing diphenhydramine (DP) and lidocaine (LD) was topically applied to the axillary or pubic areas of two volunteers; DP was also orally administered; and LD was intra-gingivally injected. Scalp, axillary, and pubic hairs were assessed using our micro-segmental analysis.
Results
The localization of DP and LD differed within individual scalp hair strands, implying DP and LD were predominantly incorporated into scalp hair via the bloodstream and via sweat/sebum, respectively, showing double-peak profiles. However, DP and LD were distributed along the shafts of axillary and pubic hairs without appearance of the double-peak profiles when the ointment had been applied to the axillary and pubic areas. The distributions of DP and LD in scalp hairs did not significantly differ according to administration routes, such as oral administration, gingival injection, and topical application.
Conclusions
Micro-segmental analysis revealed differences in the distribution profiles of drugs in hairs, and distinguished hairs with and without external contamination. These findings will be useful for understanding of the mechanism of drug uptake into hair and for estimating the circumstances for a drug use.
To prove drug‐related crimes, it is important to estimate the date on which a specific drug was ingested. Previously, we developed a method, “micro‐segmental hair analysis,” to estimate the day of ...ingestion of a single‐dose drug by segmenting a hair strand into 0.4‐mm segments, which correspond to daily hair growth. In this study, the method was improved to estimate the days of continuous drug ingestion. The subjects ingested four hay‐fever medicines (fexofenadine, epinastine, cetirizine, and loratadine) continuously (1–18 days) and chlorpheniramine as a single dose at intervals of several weeks as an internal temporal marker (ITM). The hair strands of the subjects were collected and subjected to a micro‐segmental analysis. The distribution curves of each hay‐fever medicine in a hair strand had broad peaks reflecting the number of days of drug ingestion. The positions on the curves corresponding to the first and final ingestion days of hay‐fever medicines were identified using the ITM. The positions were near the hair segments on both ends of full width at half maximum (W2) of the broad peak. When the first and final days of continuous ingestion were estimated using W2, independent of peak shape, the absolute average error from the actual ingestion days was approximately 2 days. Overall, we established a method to estimate the days of both single‐dose and continuous drug ingestions. Furthermore, the method would be useful to investigate drug ingestion history in various scenes such as drug‐related crimes and therapeutic drug monitoring.
We previously developed a method, “micro‐segmental hair analysis” to specify the day of ingestion of a single‐dose drug by cutting a hair strand into 0.4‐mm segments, which correspond to daily hair growth. In this study, the method was improved to estimate the days of continuous drug ingestion.
At temperatures above the transition temperatures, the aggregates display distinctive self-assemble structures in the presence of different additives at a defined range of concentrations.
Display ...omitted
Some low molecular weight additives can strongly influence the phase behavior of aqueous surfactant systems, and this offers an important handle to control the properties of surfactant solutions and thus to optimize the stability and performance of various formulations.
The surfactant dioctadecyldimethylammonium chloride (DODAC) self-assembles into two lamellar phases in water, the gel phase (Lβ) and the liquid crystalline phase (Lα). Here, we present approaches to tune the gel-to-liquid crystalline transition temperature (Tm) with the use of additives. The effects of urea, sodium butyrate and butyric acid on the packing behavior of DODAC were determined. The surfactant phases were characterized using polarized optical microscopy (POM), differential scanning calorimetry (DSC), and small/wide angle X-ray scattering (SWAXS).
All three additives - urea, sodium butyrate and butyric acid yield a single and stable lamellar phase. Urea and sodium butyrate have only minor effects on Tm, butyric acid gives a large decrease as it stabilizes the Lα phase with respect to the Lβ phase. From the bilayer thickness of the gel phase an interdigitated or tilted packing of the surfactant molecules is suggested. The addition of sodium butyrate gives a highly interdigitated gel structure and resulted in the transition from lamellar liquid crystal to an isotropic L3 phase.
Costimulatory signals are required for activation of immune cells, but it is not known whether they contribute to other biological systems. The development and homeostasis of the skeletal system ...depend on the balance between bone formation and resorption. Receptor activator of NF-κB ligand (RANKL) regulates the differentiation of bone-resorbing cells, osteoclasts, in the presence of macrophage-colony stimulating factor (M-CSF). But it remains unclear how RANKL activates the calcium signals that lead to induction of nuclear factor of activated T cells c1, a key transcription factor for osteoclastogenesis. Here we show that mice lacking immunoreceptor tyrosine-based activation motif (ITAM)-harbouring adaptors, Fc receptor common γ subunit (FcRγ) and DNAX-activating protein (DAP)12, exhibit severe osteopetrosis owing to impaired osteoclast differentiation. In osteoclast precursor cells, FcRγ and DAP12 associate with multiple immunoreceptors and activate calcium signalling through phospholipase Cγ. Thus, ITAM-dependent costimulatory signals activated by multiple immunoreceptors are essential for the maintenance of bone homeostasis. These results reveal that RANKL and M-CSF are not sufficient to activate the signals required for osteoclastogenesis.
During investigations of unnatural death, the time of death is generally estimated using anatomical examinations. However, it can be difficult to accurately determine the day of death, because ...postmortem changes in the body tissues can be greatly affected by the circumstances of the location of the corpse. We recently developed a method to estimate the day of drug ingestion, using micro-segmental hair analysis based on internal temporal markers (ITMs). In this method, ITMs are ingested at a specific time interval before hair collection to mark timescales within individual hair strands. A single hair strand is segmented at 0.4-mm intervals, corresponding to average daily hair growth. The day of drug ingestion is eventually estimated by calculating the distances between segments containing the drug and ITMs in a hair strand. In the present study, the method was applied to estimate the day of death. A corpse was discovered with a documented medical history of lidocaine administration for surgery 57 days before the discovery. Micro-segmental analysis of a hair plucked from the corpse was performed using lidocaine as an ITM. Lidocaine was detected at specific regions in the hair strands. The day of death was estimated using the known surgery day, the distance from the hair root to the lidocaine peak in the hair strand, and the average hair growth rate. The novel estimation method using a hair enabled us to narrow the estimated time range of death up to the day of death, unlike the conventional anatomical examination. The micro-segmental hair analysis based on drug use history can be extremely helpful in determining the time of an unnatural death.
Although T-cell immunity is thought to be involved in the prognosis of epithelial ovarian cancer (EOC) patients, immunosuppressive conditions hamper antitumour immune responses. Thus, their ...mechanisms and overcoming strategies need to be investigated.
The role of NF-κB in human EOC cells and macrophages was evaluated by in vitro production of immunosuppressive IL-6 and IL-8 by EOC cells and in vivo analysis of immune responses in nude mice implanted with human EOC cells using an NF-κB inhibitor DHMEQ.
In EOC patients, increased plasma IL-6, IL-8, and arginase were observed. The NF-κB inhibitor DHMEQ inhibited the production of IL-6 and IL-8 by EOC cell lines. Immunosuppression of human DCs and macrophages by culture supernatant of EOC cells was reversed with the pretreatment of DHMEQ. Administration of DHMEQ to nude mice implanted with human EOC resulted in the restoration of T-cell stimulatory activity of murine DCs along with the reduction of tumour accumulation and arginase expression of MDSCs. Nuclear factor-κB inhibition in tumour-bearing mice also enhanced antitumour effects of transferred murine naive T cells.
NF-κB is involved in the immunosuppression induced by human EOC, and its inhibitor may restore antitumour immune responses, indicating that NF-κB is an attractive target for EOC treatment.
Aims: The objective of this study was to investigate upon psychiatric disorders and characteristics in family members of cancer patients in Japan. Methods: We conducted a cross-sectional study from ...November 2016 to December 2017. A total of 86 families where one of partners took outpatient chemotherapy were invited to complete a questionnaire which asks about their demographic and backgroud information, health-reralted quality of life (HRQOL), family functioning, care burden and stress-coping. HRQOL was measured using the MOS 36-Item Short-Form Health Survey (SF-36), family functiong was measured using by Feetham Family Functioning Survey (FFFS) and care burden was measured using by Burden index of Caregiver (BIC-11). Data were analyzed using t-test, Perason correlations and multiple linear regressions. Results: Fifty eight (69.9%) were male and the mean age was 55.4 years. The most common cancer site was breast. The mean level of HRQOL was 49.6 and 48.9 in the physical component summary (PCS) and mental component summary (MCS), respectively, which were lower compared with the average of the general Japanese population. After adjusting for sex, age, BIC-11 score and FFFS scores, the higher discrepancy of family functioning (regression coefficient (B): -4.9, 95%CI -9.7- -0.1) and higher care burden (regression coefficient (B): -0.5, 95%CI -0.9- -0.1) were correlated with lower HRQOL in MCS. Conclusion: Our findings indicate that care burden and family functioning are factors influencing the health-related quality of life of families of cancer patients.
The nuclear spin–lattice relaxation time (T1) of lanthanum and aluminum nuclei in a single crystal of lanthanum aluminate doped with neodymium ions is studied to estimate the feasibility of the ...dynamically polarized lanthanum target applicable to beam experiments. The application of our interest is the study of fundamental discrete symmetries in the spin optics of epithermal neutrons. This study requires a highly flexible choice of the applied magnetic field for neutron spin control and favors longer T1 under lower magnetic field and at higher temperature. The T1 of 139La and 27Al was measured under magnetic fields of 0.5–2.5 T and at temperatures of 0.1–1.5 K and found widely distributed up to 100 h. The result suggests that the T1 can be as long as T1∼ 1 h at 0.1 K with a magnetic field of 0.1 T, which partially fulfills the requirement of the neutron beam experiment. Possible improvements to achieve a longer T1 are discussed.
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