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Helicobacter pyloriinfection plays a key role in the pathogenesis of H. pylori‐associated diseases, including gastroduodenal and non‐gastroduodenal diseases. A 71‐year‐old man was evaluated for a positive fecal occult blood test by upper gastrointestinal endoscopy, which revealed H. pyloriinfection, two adenocarcinomas and two gastric mucosa‐associated lymphoid tissue lymphomas. Hematological examination revealed low platelet‐count, elevated platelet‐associated immunoglobulin G and anti‐H. pyloriimmunoglobulin G antibodies. We diagnosed H. pyloriinfection complicated by simultaneous occurrence of gastric cancer, gastric mucosa‐associated lymphoid tissue lymphoma, and idiopathic thrombocytopenic purpura. These diseases were successfully treated with laparoscopy‐assisted total gastrectomy and splenectomy, and there was no evidence of recurrence for about 2 years. This is the first reported case of H. pyloriinfection complicated by these three diseases and cured with laparoscopic surgery.

Fexofenadine, a histamine H1-receptor antagonist, is approved for the treatment of pruritus associated with atopic dermatitis. The effects of fexofenadine on scratching behaviour, and plasma levels of histamine and eotaxin were assessed in a new model of atopic dermatitis. Mice fed a diet low in Mg2+and Zn2+(special diet S) were compared with mice on a normal diet (N) or diet S plus fexofenadine HCl for weeks 0-10 (S + F0-10), 0-5 (S + F0-5) or 6-10 (S + F6-10) (seven mice per group). Compared with group N, group S mice showed significantly greater scratching frequency, and plasma histamine and eotaxin concentrations; these three variables were significantly lower in group S + F0-10than in group S. Scratching frequency increased when fexofenadine was discontinued. Fexofenadine significantly reduced mast cell and eosinophil numbers. Histamine may be important in the pathological changes seen in this model of atopic dermatitis, suggesting that it might aid future development of antihistamines for the treatment of atopic dermatitis.

We aimed to develop an animal model for atopic dermatitis. HR-1 hairless mice fed a diet with reduced magnesium and zinc levels were compared with mice fed a standard diet. Skin dryness and wrinklelike changes, scratching behaviour, decreased skin water content, increased transepidermal water loss and raised blood immunoglobulin E levels were seen in the group receiving the reduced magnesium and zinc diet compared with control mice. There were no significant differences in body weight or the weight of the major organs between the two groups. Haematological examination in both groups was normal apart from increased immunoglobulin E levels in mice fed a reduced magnesium and zinc diet. These mice may be useful models of atopic dermatitis; preparation of the animals is not particularly time consuming, the reproducibility is 100%, and atopic dermatitis symptoms occur even in a specific pathogen-free environment.

A simple and efficient method for the solid-phase synthesis of benzimidazole libraries is described. Monoalkylation of various o-phenylenediamines on resin-bound bromoacetamide proceeded smoothly to give the monoalkyl resin-bound o-phenylenediamines in high yields. Subsequent cyclization of the diamines with various aldehydes afforded solid-supported benzimidazoles. Cleavage from the resin gave benzimidazoles in good yields. The present method enabled the introduction of the diversity on the benzene ring of imidazoles. Azabenzimidazoles, such as 4-azabenzimidazoles, 5-azabenzimidazoles, and purines, were also synthesized in good yields with high purities by the same procedure.

Background:The macrolide antibiotic roxithromycin is effective against acne associated with inflammation, but the mechanism by which this is achieved has not been clarified. Objective:We studied the effects of roxithromycin on the production of lipase and neutrophil chemotactic factor by Propionibacterium acnesin vitro. Results:Roxithromycin significantly inhibited the production of lipase and neutrophil chemotactic factor by P. acnesat a concentration one eighth of the MIC, at which the growth curve of P. acnesis not affected. Conclusion:One mechanism of the effectiveness of roxithromycin in acne therapy is thought to be the inhibition of bacterial lipase and neutrophil chemotactic factor production by P. acnes.

Roxithromycin, a macrolide antibiotic, is used in the treatment of acne vulgaris, although there have been no reports on its concentration in lesions when administered orally. We investigated the concentration of roxithromycin in acne vulgaris lesions in five patients who received 150 mg roxithromycin orally twice daily for 2 weeks. The mean concentration of roxithromycin in the lesions was 0.54 μg/ml. These results suggest that roxithromycin accumulates at therapeutic levels in the pilosebaceous system.

The objective of the study was to investigate the pharmacological action of roxithromycin, an oral macrolide antibiotic. The effects of roxithromycin on the cytokine-induced expression of endothelial leukocyte adhesion molecule (E-selectin) and intracellular adhesion molecule (ICAM)-1 on endothelial cells of the dermal microvasculature were investigated in vitrousing flow cytometry. Roxithromycin at a concentration of 0.5 μg/ml, which is lower than the therapeutic plasma concentration (ordinary daily dose, 150–300 mg), significantly inhibited the expression of E-selectin and ICAM-1 on endothelial cells of the dermal microvasculature induced by tumour necrosis factor-α. We conclude that roxithromycin may exert its anti-inflammatory action by inhibition of the in vivoexpression of adhesion molecules on dermal microvascular endothelial cells.

This study is devoted to examining an adaptive sorbent for the combined desulfurization/denitration (DeSOx/DeNOx) process reported in work by Xu et al. (Trans. Inst. Chem. Eng. 1999, 77, Part B, 77−87). The so-called powder-particle fluidized bed (PPFB) is used by the process so that SOx in flue gas is absorbed by a continuously supplied fine DeSOx sorbent and NOx is reduced to N2 by ammonia under the catalysis of a coarse DeNOx catalyst, the fluidization medium particles (FMP). Experiments were conducted in a laboratory-scale PPFB reactor by using model flue gases containing SO2 and NO. It was found that the sodium carbonate supported by fine alumina particles (Na2CO3/Al2O3) had not only a high efficiency in absorbing SO2 but also little negative effect upon the simultaneous NOx reduction of the process. Using a DeNOx catalyst, such as V2O5·WO3/TiO2 or WO3/TiO2, to catalyze the DeNOx reactions, high SO2 absorption and NO reduction in excess of 95% were achieved for model gases free of CO2 at stoichiometric ratios of SO2 to sorbent (Na/S = 2.0) and NH3 to NO (NH3/NO = 1). As for the simulated flue gas SO2−NO−H2O−N2−air with an oxygen fraction of 2 vol % and a water vapor fraction of 5 vol %, such high removals of SO2 and NO were found available even in a shallow PPFB with a static catalyst packing height of 0.1 m. By using silica sand as FMP, the pure SO2 absorption by the sorbent Na2CO3/Al2O3 was also examined with respect to various influential factors, such as reaction temperature (523−673 K), flue gas composition (oxygen fraction and water vapor fraction), sorbent diameter, and operating conditions (gas velocity and FMP bed height).

An in vitrostudy was carried out to investigate the effect of clarithromycin, a new oral macrolide, on neutrophil reactive oxygen species generation and chemotaxis. It was found that neutrophil-generated 02−, H202and OH· levels were significantly increased by clarithromycin at concentrations of 50 μg/ml (P< 0.05). The drug also significantly increased chemotaxis (P< 0.05). These results indicate that clarithromycin may enhance the activation of neutrophils in vivo.

Comedonal bacteria, Propionibacterium acnes, P. granulosum and coagulase-negative staphylococci (CNS) seem to play an important initiating role in the inflammatory process by producing neutrophil chemotactic factors. The attracted neutrophils, after phagocytosis, release inflammatory factors such as reactive oxygen species (ROS). We investigated the effects of minocycline at subminimal inhibitory concentrations (sub-MIC), i.e. one-tenth MIC, on the production of human neutrophil chemotactic factors in comedonal bacteria, and on several inflammatory parameters of neutrophils, including neutrophil phagocytosis and generation of ROS (O2-, H2O2, O $${\text{H}}^{\text{.}} $$ ). ROS generation in a cell-free, xanthinexanthine oxidase system was also assessed. Production of neutrophil chemotactic factors in all strains of P. acnes, P. granulosum and CNS were significantly suppressed by sub-MIC minocycline. Sub-MIC minocycline effectively reduced three kinds of neutrophil-generated ROS (O2-, H2O2, O $${\text{H}}^{\text{.}} $$ ). However, neutrophil phagocytosis and the ROS generated in a cell-free system were not markedly changed in the presence of sub-MIC minocycline. The results suggest that sub-MIC minocycline has an anti-inflammatory effect by inhibiting the production of neutrophil chemotactic factors in comedonal bacteria as well as ROS generated by neutrophils in the inflammatory process of acne.

Lipid peroxide levels, the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px), and the development of tanning in the skin of C57 BL/6 mice were assessed for long periods, from very early to late stages, after acute or chronic UVB irradiation. Acute UVB irradiation produced an increase in lipid peroxide levels that peaked 18 h after irradiation, after which the levels declined to a minimum 2–3 days after irradiation and then gradually rose to baseline. Chronic irradiation caused the lipid peroxide level to fall to a minimum at 0.5–1.0 weeks, after which it gradually returned to baseline by the third week. SOD and GSH-Px activities decreased sharply after acute irradiation, reaching a minimum 18 h after irradiation. Following chronic irradiation, these enzyme levels peaked after 0.5 weeks, and thereafter declined gradually to the original levels 3 weeks after irradiation. In contrast, catalase activity did not change significantly. Tanning began to increase at 1.5 weeks after irradiation, with an accelerated rate of increase from the third week. Although UVB has been reported only to decrease or impair reactive oxygen species (ROS) scavenging enzyme activity, we postulate the following from our results: (1) the increase in lipid peroxide levels observed after irradiation was due to UVB-induced ROS; (2) the parallel decrease in enzyme activities may have been due to inactivation by ROS; (3) the decrease in lipid peroxide levels following the peak at 18-h resulted from the scavenging effect of increasing SOD and GSH-Px activities, and (4) the increase in these two enzyme activities was the result of their induction by the increased lipid peroxides or ROS. In addition, these results seem to suggest a possible correlation of melanogenesis with UVB-induced ROS.

On the basis of recent reports that keigai-rengyo-to (TJ-50), an oral Japanese Kampo (herb) medicine, is clinically effective in treating acne, and that tetracyclines are effective against acne by acting directly as an antioxidant on infiltrated neutrophils, we investigated the effect of TJ-50 on the generation of reactive oxygen species (ROS), using human neutrophils and a cell-free, xanthine-xanthine oxidase system. The species investigated were superoxide radical anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH·). In addition, neutrophil chemotaxis, phagocytosis and calcium concentration, [Ca2+]i in neutrophils were also assessed. TJ-50 significantly decreased neutrophil-generated O2-, H2O2and OH· in a dose-dependent manner. Three kinds of ROS generated in the cell-free system were also reduced in the presence of TJ-50. On the other hand, the medicine did not markedly affect neutrophil chemotaxis, phagocytosis or [Ca2+]i in neutrophils. Our results indicate that the clinical effectiveness of TJ-50 in the treatment of acne may be due partly to its antioxidant action on infiltrated neutrophils.

Metronidazole is clinically effective in treating not only rosacea but also acne inflammation. Yet it is generally considered not to be very effective in inhibiting the growth of anaerobic Propionibacterium acnes. We report here our investigation into the synergistic effects of metronidazole and palmitoleic acid on the anaerobic growth of P. acnes as well as on human neutrophil functions, including the generation of reactive oxygen species (ROS). Both metronidazole and palmitoleic acid, when used alone, only slightly inhibited the growth of P. acnes, and no significant decrease in human neutrophil functions, including the generation of ROS, was observed. But metronidazole used in the presence of palmitoleic acid markedly inhibited the anaerobic growth of P. acnes and decreased ROS generation by neutrophils. However, ROS generated in the xanthine-xanthine oxidase system were not affected. Metronidazole was shown to be clinically effective by decreasing neutrophil-generated ROS at the sites of inflammation with the aid of palmitoleic acid, which is generally present in human skin. By inhibiting oxidative tissue injury under in vivo conditions, treatment with metronidazole results in remarkable improvement of rosacea and acne.

It has been shown that acne, hyperpigmentation and lentigo malignant are more or less related pathogenetically to reactive oxygen species (ROS). It has recently been reported that azelaic acid is effective in treating these conditions and that it possesses anti-enzymatic and anti-mitochondrial activity, including cytochrome-P450 reductase and 5a-reductase in microsomal preparations with nicotinamide adenine dinucleotide phosphate (NADPH). We therefore investigated the effects of azelaic acid on human neutrophil functions, such as chemotaxis, phagocytosis and ROS generation. ROS generation in a cell-free system was also assessed. The results revealed that neutrophil chemotaxis and phagocytosis as well as ROS generated in a xanthine — xanthine-oxidase system were not significantly changed in the presence of azelaic acid. However, azelaic acid markedly decreased O2-and OH generated by neutrophils. It may be concluded that the reported clinical effectiveness of azelaic acid is partly due to its inhibitory action on neutrophil-generated ROS, leading to a reduction both in oxidative tissue injury at sites of inflammation and in melanin formation.

We investigated the effects of proximal modulators of cytokines, tyrosine kinase (TK), and protein kinase C (PKC) on reactive oxygen species (ROS) generation and the induction of scavenging enzymes, superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) of human neutrophils and lymphocytes, by using IL1-α, TNF-α, and IFN-γ and neutralizing antibodies to these cytokines. Inhibitors of TK (ST638 and herbimycin) or PKC (H-7, calphostin, and staurosporine) were also used. The results revealed that both O−2generation stimulated by five different agents (opsonized zymosan, A23187, PAF, PMA, and fMLP) and the inductions of all three scavenging enzymes were potentiated by priming with TNF-α. In contrast, both O−2generation and enzyme induction were attenuated by priming with IL1-α, with the exception of PMA-stimulated O−2generation. IFN-γ decreased O−2generation but increased scavenging enzyme induction. Antibodies to all three cytokines and all the TK and PKC inhibitors decreased O−2stimulated by most agents, but markedly enhanced O−2levels stimulated by PAF. Induction of all three enzymes was enhanced equally by low concentrations of each of the three anticytokine antibodies, while each of the TK or PKC inhibitors decreased induction of SOD and GSH-Px and increased catalase induction. These results suggest that both ROS generation and scavenging enzyme induction are controlled in complex ways by the actions of these three proximal mediators. This supports our hypothesis that disturbances in the regulation of early events of cell activation can lead to oxidative tissue injury.

Our aim in this study was to determine the mediastinal areas where lymphadenectomy should be done at the time of surgical resection of clinical stage I lung cancer. Between 1984 and 1994, 575 patients with clinical stage I non-small-cell lung cancer underwent lobectomy and systematic mediastinal lymphadenectomy. Mediastinal lymph nodes were pathologically positive for disease in 79 patients (14%), and positive nodes appeared normal intraoperatively in 54 patients (68%). Thirty-three percent of those patients with positive N2 (mediastinal) nodes had negative lobar (N1) nodes. In cancer of the right upper lobe, all N2 cases had the lymph node metastases in the superior mediastinal compartment. In cancer of the right middle lobe, all N2 cases but one had the metastases in subcarinal or anterior mediastinal nodes. In cancer of the right lower lobe, all N2 cases but one had the metastases in subcarinal nodes. In cancer of the left upper lobe, all N2 cases had the lymph node metastases in the subaortic compartment. In cancer of the left lower lobe, all N2 cases but one had the lymph node metastases in the subcarinal area or subaortic compartment. In conclusion, systematic staging of mediastinal lymph nodes is necessary for all patients with resectable clinical stage I lung cancer. The location of the primary tumor determines the mediastinal areas where lymphadenectomy should be done to examine all lymph nodes. (J Thorac Cardiovasc Surg 1997;113:248-52)

The effects of ofloxacin, ciprofloxacin and balofloxacin on the reactive oxygen species (ROS) levels generated by human neutrophils was examined in vitro; ROS generated in a cell-free, xanthine–xanthine oxidase system was also assessed. The species investigated were superoxide radical anion (O2−), hydrogen peroxide (H2O2) and hydroxyl radical (OH·). Both ofloxacin and ciprofloxacin markedly decreased the levels of O2−, H2O2and OH· generated by human neutrophils. On the other hand, these drugs did not affect any of the ROS examined in the xanthine-xanthine oxidase system. Balofloxacin showed no significant effect on ROS generated by either system. The present study indicates that ofloxacin and ciprofloxacin may exert an anti-inflammatory action by reducing the potent ROS species excessively generated by neutrophils at the sites of inflammation.

It has recently been shown that gabexate mesilate inhibited human neutrophil functions including chemotaxis and reactive oxygen species production. In the present study, the effects of gabexate mesilate on phagocytosis by human neutrophils in vitrowere investigated. Gabexate mesilate significantly enhanced neutrophil phagocytosis in a dose-dependent manner. This characteristic of gabexate mesilate may facilitate protection against infecting micro-organisms, although the inhibition of reactive oxygen species production by neutrophils may be a disadvantage for host-defense against infection.

Neutrophils accumulated in the lung are thought to play a key role in the pathogenesis of adult respiratory distress syndrome and interstitial pneumonia following bone-marrow transplantation. The effects of gabexate mesilate on several aspects of human neutrophil function have been investigated. Gabexate mesilate significantly decreased both the generation of reactive oxygen species (O2−, H202, OH·) by neutrophils and neutrophil chemotaxis. In contrast, the drug did not affect the levels of reactive oxygen species generated by a cell-free reactive-oxygen-species generating system. Intracellular calcium concentrations in neutrophils stimulated by f-Met-Leu-Phe were decreased in the presence of gabexate mesilate. These data suggest that the reduction in reactive-oxygen-species production and neutrophil chemotaxis by gabexate mesilate may contribute to the effectiveness of the drug in adult respiratory distress syndrome and interstitial pneumonia after bone-marrow transplantation. The suppression of the increase in intracellular calcium concentration may at least be responsible for the inhibition of these neutrophil functions by gabexate mesilate.

The in vitrosusceptibility of methicillin-resistant Staphylococcus aureus(MRSA)to nadifloxacin and seven other fluoroquinolones (norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin and sparfloxacin) was evaluated. The MRSAisolates were isolated from 114 skin infections between 1991 and 1994. Nadifloxacin exhibited the lowest minimum inhibitory concentration and there were no MRSAisolates resistant to nadifloxacin, while there were some resistant to all of the other seven fluoroquinolones. The minimum concentrations of these drugs needed to cause 50% inhibition of the isolates increased dramatically from 1991 to 1992, but has hardly changed since 1992.

The effect of roxithromycin (ROM), a new oral semisynthetic macrolide, on the generation of reactive oxygen species (ROS), using human neutrophils and a cell-free, xanthine-xanthine oxidase system was examined. The species investigated were the superoxide radical anion (O2−), hydrogen peroxide (H2O2), and the hydroxyl radical (OH·). ROM effectively inhibited the generation of O2−, H2O2and OH· by human neutrophils. On the other hand, the drug did not markedly affect the ROS levels generated in the xanthine-xanthine oxidase system. The present study indicates that ROM may exert an anti-inflammatory action by inhibiting neutrophil oxygen radical generation at the sites of inflammation.

On the basis of reports that erythromycin is effective in the treatment of acne, we investigated whether roxithromycin (ROM), a new derivative of erythromycin, might also be effective in treating acne. Roxithromycin was administered to 30 patients with acne for 8 weeks. General improvement was assessed 8 weeks after the initiation of the therapy with a six-graded scale as follows; 1: good improvement, 2: moderate improvement, 3: slight improvement, 4: no change, 5: worsening, and 6: no assessment. The percentage of good or moderate improvement was 73.3%, and that of good improvement alone was 20.0%. Our results suggest that ROM is effective in the treatment of acne.

The applicability of a novel enzymatic assay for quantifying skin surface lipids was investigated experimentally. The standard curves for the assays of glycerol esters, free fatty acids, and cholesterol and its esters were linear over a wide range of lipid concentrations, which ensures the accuracy of measurements. The assay system also showed good simultaneous reproducibility. There were significant positive correlations (P <0.001) between the quantities of glycerol esters, free fatty acids, and cholesterol and its esters sampled from the skin surface of women when measured by the enzymatic assay compared with the gas chromatographic method. The enzymatic assay was applied to studies of the relationships between age, acne and menstrual cycle, and skin surface lipids in women. The quantities of glycerol esters and free fatty acids reached peaks in females in their twenties and thirties. Increased quantities of glycerol esters, free fatty acids, and cholesterol and its esters were observed in women with acne compared with women without acne. Among the women with acne, those in the premenstrual phase of the menstrual cycle showed increased levels of glycerol esters, free fatty acids, and cholesterol and its esters compared with those in the menstrual phase. The results suggest that the enzymatic method is a satisfactory new technique for the quantification of skin surface lipids.

Neutrophils accumulated in the lung are thought to play a pivotal role in the pathogenesis of host auto-injury such as adult respiratory distress syndrome (ARDS). We investigated the effect of prostaglandin E1(PGE1) on several aspects of human neutrophil function. PGE1significantly decreased reactive oxygen species (ROS), (O2−, H2O2, OH·) generation by neutrophils as well as neutrophil phagocytosis and chemotaxis. In contrast, the drug did not affect the levels of ROS generated by a cell-free ROS generating system. In addition, intracellular calcium concentrations ([Ca2+]i) in neutrophils stimulated by f-Met-Leu-Phe were decreased in the presence of PGE1. These data suggest that the reduction in ROS production and neutrophil phagocytosis and chemotaxis by PGE1may contribute to the effectiveness of the drug in host auto-injury including ARDS. The suppression of the increase in [Ca2+]i may at least be responsible for inhibition of these neutrophil functions by PGE1.

The most common pathogen causing skin infections is Staphylococcus aureusand the incidence of multiply resistant strains of S. aureushas been increasing. The in vitrosusceptibility of 130 isolates of S. aureusto 19 antimicrobial agents: ampicillin (ABPC), methicillin, cefaclor, cefpodoxime proxetil, gentamicin, erythromycin, clindamycin, minocycline, vancomycin, fusidic acid, norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin, nadifloxacin and grepafloxacin, was evaluated by agar dilution tests. The S. aureusisolates were isolated from 130 patients with skin infections in 1994. The proportion of methicillin-resistant S. aureusisolates among the strains isolated was 19.2%. The concentration needed to inhibit 50% of the isolates was 3.13 mg/ml or less for all of the drugs, but the concentration needed to inhibit 90% of isolates was over 12.5 μg/ml, except in the cases of minocycline, vancomycin, fusidic acid, tosufloxacin and nadifloxacin. Tosufloxacin and nadifloxacin had the lowest minimum inhibitory concentrations. None of the S. aureusstrains was resistant to nadifloxacin.

Recent reports indicate that nadifloxacin is an effective therapy for acne vulgaris and has a mechanism of action similar to that of the tetracyclines which act directly as antioxidants against infiltrated neutrophils. The effects of nadifioxacin on neutrophil functions, including the generation of reactive oxygen species, chemotaxis and phagocytosis were investigated. Nadifloxacin reduced the numbers of superoxide radical anions (O2−) and hydroxyl radicals (OH·) generated by neutrophils. The drug did not, however, significantly inhibit neutrophil chemotaxis and phagocytosis nor did it decrease the levels generated in a cell-free, xanthine–xanthine oxidase system. These results indicate that the clinical effectiveness of nadifloxacin may be partly due to its inhibitory action on the generation of O2−and OH· by neutrophils leading to a reduction in oxidative tissue injury.

Seborrhoea and acne are exclusively human diseases and sebaceous gland differentiation is species specific. Therefore, fundamental research on human sebaceous cell function and control requires human in vitro models. The human sebocyte culture model, introduced in 1989, has been used in several studies to elucidate sebaceous gland activity and its regulation at the cellular level. Cultured human sebocytes have been shown to preserve important sebocytic characteristics, although they undergo an incomplete terminal differentiation in vitro. In vitro synthesis of free fatty acids without bacterial involvement and marked interleukin 1α expression at the mRNA and protein levels with no further induction by lipopolysaccharides lead to the assumption that human sebocytes may initiate acne lesions by an intrinsic mechanism. Androgens affected sebocyte activity in vitro in a manner dependent on the localization of the sebaceous glands. In vitro stimulation of sebocyte proliferation by androgens could be completely abolished by spironolactone. Cultured sebocytes strongly expressed type 1 5α-reductase and metabolized testosterone to androstenedione, 5α-androstanedione, 5α-dihydrotestosterone, androsterone and 5α-androstanediol, whereas the levels of 5α-reductase activity were probably not feedback regulated. 4,7β-Dimethyl-4-aza-5αcholestan-3-one, a type 1 5α-reductase inhibitor, induced an early, marked down-regulation of 5α-reductase activity in human sebocytes in vitro, while hydrofinasteride, a type 2 inhibitor, required 103-fold higher concentrations to induce similar effects. Stimulation of sebocyte proliferation by insulin, thyroid-stimulating hormone and hydrocortisone indicates that the hormonal control of the sebaceous gland could be a complex mechanism. Retinoids inhibited sebocyte proliferation in a dose-dependent manner and down-regulated lipid synthesis and sebocyte differentiation in vitro. Isotretinoin was the most potent compound. On the other hand, vitamin A was found essential for sebocyte activity and differentiation in vitro and could be partially substituted by synthetic retinoids. The inhibitory effect of isotretinoin on sebocyte proliferation was barely affected by the presence of vitamin A. The low persistent isotretinoin levels or, more likely, the considerably elevated tretinoin concentrations detected in human sebocytes after treatment with isotretinoin in vitro may be responsible for the inhibitory effect of this compound on sebocyte activity.

The purpose of this study was to investigate the possible role of reactive oxygen species (ROS) generated by neutrophils in mediating acne inflammation. Antibiotics used for the treatment of acne significantly inhibited ROS generated by neutrophils, when compared to other antibiotics. Metronidazole, which is effective in the treatment of acne, markedly inhibited ROS generated by neutrophils. The drug is known to have no significant effect on the growth of Propionibacterium acnes. The proportion of linoleic acid is markedly decreased in acne comedones. Linoleic acid significantly suppressed ROS generated by neutrophils. The ability of neutrophils to produce ROS was significantly increased in patients with acne inflammation. These results seem to reveal the involvement of ROS generated by neutrophils in the disruption of the integrity of the follicular epithelium, which is responsible for inflammatory processes of acne.

Background:A human sebaceous gland culture system is very useful in studying the functions of the sebaceous glands at the cellular level. On the other hand, the success rates for culture systems and the experimental results from these human culture systems exhibit significant fluctuations, depending on the condition of the donor skin. Objective:The purpose of this study was to establish a stable culture system in order to investigate the functions of the sebaceous glands under uniform conditions. Methods:Sebaceous glands from the auricles of 5-week-old hamsters were isolated and seeded onto a 3T3 cell feeder layer. The proliferation, lipid production and response to androgens of these sebaceous-gland-derived cells (SGDC) were then examined. Results:The SGDC showed outgrowth, formed colonies and became confluent in a 35-mm dish culture after 14 days in primary culture. The amount of intracellular lipids significantly increased following the peak of the cell proliferation. The composition of the intracellular lipids from the hamster SGDC was identical to human SGDC, except that the hamster SGDC did not contain any squalene. Testosterone and 5α-dihydrotestosterone markedly stimulated the proliferation of these SGDC in a dose-dependent manner. Conclusion:This tissue culture system will be a useful tool for the study of sebaceous gland function at the cellular level.