Paediatric morphoea: a holistic review. Part 2: diagnosis, measures of disease activity, management and natural history.

Paediatric morphoea is a debilitating fibrosing disorder of uncertain aetiology, affecting the skin and subcutaneous tissues. Defining optimum management strategies in paediatric morphoea remains an ongoing challenge, owing to the varied presentations and a relative paucity of paediatric-specific studies. We performed a literature search on PubMed, MEDLINE and Google Scholar, using keywords such as 'pediatric morphea', 'juvenile localised scleroderma' and 'juvenile systemic sclerosis'. Relevant studies, including randomized trials, reviews of standard current guidelines and original research articles, were selected and results analysed before summarizing them. In Part 1 of this review, we described the epidemiology, aetiopathogenesis and clinical classification; in this part, we discuss the diagnosis, markers of disease activity, management and natural history in paediatric morphoea.

The clinicoaetiological, hormonal and histopathological characteristics of melasma in men.

BACKGROUND: Melasma is relatively uncommon in males, and there is a paucity of data on male melasma, including its clinical pattern, triggering factors, endocrine profile and histopathological findings. AIM: To characterize the clinical findings and aetiological factors, including hormonal and histopathological features, of male melasma. METHODS: Male patients with melasma and age- and sex-matched healthy controls (HCs) were recruited. Demographic profile, risk factors, clinical pattern and Wood lamp findings of patients were recorded. Sera were obtained from patients and HCs to determine hormone levels. Biopsy specimens were obtained from lesional and adjacent nonlesional skin. RESULTS: In total, 50 male patients with melasma and 20 HCs were recruited into the study. Mean age of patients was 27.58 ± 4.51 years. The most common clinical pattern of melasma was malar, which occurred in 52% of cases. Positive family history was present in 16% of patients, while 34% had disease aggravation with sun exposure and 62% used mustard oil for hair growth and/or as an emollient. Wood lamp examination revealed epidermal-type melasma in 54% of patients. There were no significant differences in hormone levels between patients and HCs. Histologically, epidermal melanin, elastotic degeneration, vascular proliferation and mast cells were more pronounced in lesional compared with nonlesional skin. Absent to weak expression of oestrogen receptors, progesterone receptors and stem cell factor was observed in lesional skin. CONCLUSION: Ultraviolet light and mustard oil are important causative factors in male melasma. Although stress and family history may contribute, hormonal factors possibly have no role. Quantitative analysis of immunohistochemical markers would provide insight in understanding the pathogenesis of melasma.

Constituents of Pterocarpus marsupium: an ayurvedic crude drug.

Five new flavonoid C-glucosides, 6-hydroxy-2-(4-hydroxybenzyl)-benzofuran-7-C-beta-d-glucopyranoside (1), 3-(alpha-methoxy-4-hydroxybenzylidene)-6-hydroxybenzo-2(3H)-furanone-7-C-beta-d-glucopyranoside (2), 2-hydroxy-2-p-hydroxybenzyl-3(2H)-6-hydroxybenzofuranone-7-C-beta-d-glucopyranoside (4), 8-(C-beta-d-glucopyranosyl)-7,3',4'-trihydroxyflavone (5) and 1,2-bis(2,4-dihydroxy,3-C-glucopyranosyl)-ethanedione (6) and two known compounds C-beta-d-glucopyranosyl-2,6-dihydroxyl benzene (7) and sesquiterpene (8), were isolated from an aqueous extract of the heartwood of Pterocarpus marsupium. The structure has been established using spectroscopic data.

Protective effect of acorus calamus against acrylamide induced neurotoxicity.

Exposure of rats to acrylamide (ACR) caused hind limb paralysis in 58% of the animals on day 10 and decreased behavioural parameters, namely distance travelled, ambulatory time, stereotypic time and basal stereotypic movements compared with the control group. These rats also had a decrease in the reduced glutathione (GSH) content and glutathione-S-transferase (GST) activity in the corpus striatum and an increase in striatal dopamine receptors, as evident by an increase in the binding of 3H-spiperone to striatal membranes. Treatment with the ethanol:water (1:1) extract of the rhizomes of Acorus calamus (AC-002) increased the GSH content and GST activity in the corpus striatum while insignificant changes were observed in other parameters. Rats treated with ACR and AC-002 in combination had a lower incidence of paralysis (18%) compared with those treated with ACR alone on day 10 of the experiment. The rats also showed a partial recovery in other behavioural parameters. The levels of GSH content and GST activity increased in the corpus striatum, while the dopamine receptors decreased compared with the ACR treated rats. The results suggest that the neurobehavioural changes produced by ACR may be prevented following treatment with Acorus calamus rhizomes.

Specific inhibiting characteristics of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine 'Chuanxiong,' on platelet thrombus formation under high shear rates.

We have investigated the effects of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine Chuanxiong, on platelet thrombus formation under flow conditions. We demonstrate herein that tetramethylpyrazine inhibits shear-induced platelet aggregation under relatively high shear rate of 10,800 s(-1) with modest inhibition of those occurring under relatively low shear rate of 1200 s(-1) by using optically modified cone-plate viscometer. We also demonstrate that platelet activation induced by shearing in the absence of exogenous platelet-activating agents such as ADP as evidenced by P-selectin surface expression and microparticle release detected by quantitative flow cytometry was also inhibited by tetramethylpyrazine. Moreover, we also demonstrate platelet thrombus formation on the collagen and von Willebrand factor (vWF) surface at high shear rates without significant influences on those occurring under relatively low shear rates. Because platelet thrombus formation occurring under high shear rates is known to be mediated by the vWF interaction with platelet receptor proteins GP Ibalpha and GP IIb/IIIa, we speculated that tetramethylpyrazine exerts antiplatelet effects by inhibiting the vWF-mediated process of platelet thrombus formation. Our findings, indicating the unique antiplatelet characteristics of tetramethylpyrazine, selectively inhibiting the platelet thrombus formation under high shear rates, provide good reasons for developing chemical analogs having biological functions similar to or more potent than those of tetramethylpyrazine as antiplatelet agents having unique biological functions.

Hepatoprotective activity of indigtone--a bioactive fraction from Indigofera tinctoria Linn.

A bioactive fraction, indigtone (FA), obtained by fractionation of a petroleum ether extract of the aerial parts of Indigofera tinctoria, showed significant dose related hepatoprotective activity against CCl(4) induced liver injury in rats and mice. Hexobarbitone induced 'sleeptime', zoxazolamine induced 'paralysis time', levels of transaminases, bilirubin and total protein in serum were employed as indices of liver injury. Pre and post treatment with FA significantly reversed the majority of the parameters altered by the hepatotoxin. This indicated the preventive and restorative effect of FA in the process of CCl(4) induced liver damage. The fraction possessed a high therapeutic ratio, as no mortality was observed up to a dose of 2 g/kg p.o. in mice.

Severe metabolic acidosis and heart failure due to thiamine deficiency.

We report the case of a male patient with severe metabolic acidosis and heart failure caused by thiamine deficiency. He was admitted in August 1998 to the Tokai University Oiso Hospital because of severe dyspnea. The patient was diagnosed with heart failure and metabolic acidosis of unknown causes based on arterial blood gas analysis, chest x ray, and ultrasonic echocardiographic examinations. Our previous experience in treating a patient with thiamine deficiency caused by total parenteral nutrition without thiamine supplementation suggested that this patient was deficient in thiamine. The serum thiamine level was low and the lactate level was high. After intravenous administration of thiamine, the acidosis and heart failure disappeared. Dietary analysis showed that thiamine intake was low (0.32 mg/1000 kcal/d). Thiamine deficiency should be included in the differential diagnosis when encountering cases of heart failure with severe metabolic acidosis, even in developed countries.

Oral hyposensitization in patients with contact dermatitis from Parthenium hysterophorus.

Parthenium hysterophorus is the commonest cause of airborne contact dermatitis in northern India. Treatment is mostly palliative and consists of repeated courses of antihistamines and topical and/or systemic corticosteroids. We have evaluated the effect of oral hyposensitization as an alternative therapeutic modality. In 70% of those patients who completed the study, there was a gradual improvement in their clinical status, as evident from a fall in their clinical severity score for eczema. 30% of patients had an exacerbation during the course of the study and hence hyposensitization in them was stopped. Patients tolerated therapy well and no significant side-effects were seen, except for abdominal pain, 'heartburn' and cheilitis.

Antiinflammatory activity and chemical composition of extracts of Verbena officinalis.

In an attempt to locate the biologically active fraction(s) of the plant Verbena officinalis Linn. (Verbenaceae), a preliminary screening of successive petroleum ether, chloroform and methanol extracts of aerial parts for antiinflammatory activity using carrageenan paw oedema model was carried out. All three extracts were found to exhibit antiinflammatory activity with the chloroform extract being the most active. Chemical investigations of petroleum ether and chloroform extracts led to the isolation of beta-sitosterol, ursolic acid, oleanolic acid, 3-epiursolic acid, 3-epioleanolic acid, and minor triterpenoids of derivatives of ursolic acid and oleanolic acids. Chromatographic purification of the methanol extract yielded two iridoid glucosides, verbenalin and hastatoside, a phenylpropanoid glycoside, verbascoside and beta-sitosterol-D-glucoside.

Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase.

Silymarin, a mixture of flavonolignans, comprised mainly of three isomers, silybin, silydianin and silychristin isolated from the fruits of Silybum marianum, is currently in therapeutic use as a hepatoprotective agent. Silymarin on evaluation exhibited significant antiinflammatory and antiarthritic activities in the papaya latex induced model of inflammation and mycobacterial adjuvant induced arthritis in rats. Results of the study indicate its action through inhibition of 5-lipoxygenase for antiinflammatory and antiarthritic activities.

Antihepatotoxic activity of Swertia chirata on paracetamol and galactosamine induced hepatotoxicity in rats.

The extracts of Swertia chirata were evaluated for antihepatotoxic activity using paracetamol and galactosamine models. The methanol extract of the whole plant was found active at a dose of 100 mg/kg i.p. On fractionating this extract into chloroform soluble and butanol soluble fractions, the activity was retained in the chloroform soluble fraction which was most active at a dose level of 25 mg/kg i.p. with overall protection of 81% and 78% against paracetamol and galactosamine, respectively. The butanol soluble fraction, rich in bitter secoiridoids, was devoid of significant activity. The protective effect observed against these two hepatotoxins which are different in their mechanisms of inducing hepatotoxicity, suggests broader and non-specific protection of the liver against these two toxins by non-bitter components of Swertia chirata.

Antihepatotoxic activity of Swertia chirata on carbon tetrachloride induced hepatotoxicity in rats.

The methanol extract of Swertia chirata was evaluated for antihepatotoxic activity against carbon tetrachloride induced liver toxicity in experimental rats. The extract was found to be active and on fractionation into butanol soluble and chloroform soluble fractions, the activity was traced and found more profound in the chloroform soluble fraction. The butanol soluble bitter rich fraction showed marginal activity. The results based on biochemical estimations have been expressed statistically and are additionally supported by histopathological examination of the liver of experimental rats and pentobarbitone induced sleep time studies in mice.

Preparation of peptides which mimic glycosphingolipids by using phage peptide library and their modulation on beta-galactosidase activity.

We describe the use of a phage-displayed random pentadecamer peptide library for searching glycosphingolipid mimicking peptides. Two phage clones (AD-1 and AD-2) were selected by biopanning using monoclonal antibody AD117m, directed to lactotetraosylceramide (Lc4Cer). The amino acid sequences of the selected clones showed high homology (VPPXFXXXY) in 9-mer. Three phage clones were selected by using monoclonal antibody H11, directed to neolactotetraosylceramide (nLc4Cer), the linkage isomer of Lc4Cer, and the displayed amino acid sequences were compared. One of these peptides showed the same amino acid sequence as that of AD-2 except for one amino acid substitution. Pentadecamer, 9-mer and point mutated 9-mer peptides were synthesized on the basis of the displayed amino acid sequences. Binding activity of the peptides to the monoclonal antibodies or Ricinus communis lectin showed that 9-mer peptides are enough to mimic the epitope carbohydrate structure. Furthermore, six of the synthesized peptides inhibited Jack bean beta-galactosidase activity towards nLc4Cer at a high concentration of the enzyme, whereas at lower enzyme concentrations some peptides showed potent activation of the enzyme activity. This is the first report of carbohydrate mimicking peptides which modulate glycosidase activity.

Regression of increased left ventricular masses in elderly hypertensive patients on lisinopril as assessed by magnetic resonance imaging.

RATIONALE AND OBJECTIVES: We investigated, using magnetic resonance imaging, whether the addition of lisinopril could reduce increased left ventricular (LV) masses in hypertensive patients whose blood pressure was well controlled with nifedipine. METHODS: Fourteen hypertensive patients being treated with nifedipine and having an interventricular septum thickness of more than 12 mm were studied. Half of them were given 5 mg lisinopril, and the others were not. Short-axis images of the left ventricle from the base to the apex were obtained by a standard spin-echo pulse sequence. The entire LV mass was calculated from the area of short-axis slices of the left ventricle multiplied by slice thickness. RESULTS: Blood pressure fell slightly and almost equally in both groups. The LV mass and LV mass index showed a significant decrease in the lisinopril-treated group but not in the control group. CONCLUSION: Results demonstrate the effectiveness of lisinopril in reducing increased LV masses, at least in combination with nifedipine.

Hepatoprotective activity of Apium graveolens and Hygrophila auriculata against paracetamol and thioacetamide intoxication in rats.

Seeds of Apium graveolens L. (Apiaceae) and Hygrophila auriculata (K. Schum.) Heine (Syn. Astercantha auriculata Nees, Acanthaceae) are used in Indian systems of medicine for the treatment of liver ailments. The antihepatotoxic effect of methanolic extracts of the seeds of these two plants was studied on rat liver damage induced by a single dose of paracetamol (3 g/kg p.o.) or thioacetamide (100 mg/kg, s.c.) by monitoring several liver function tests, viz. serum transaminases (SGOT and SGPT), alkaline phosphatase, sorbitol dehydrogenase, glutamate dehydrogenase and bilirubin in serum. Furthermore, hepatic tissues were processed for assay of triglycerides and histopathological alterations simultaneously. A significant hepatoprotective activity of the methanolic extract of the seeds of both the plants was reported.

[Bacteriological, pharmacokinetic and clinical studies on biapenem (L-627) in the pediatric field].

Antibacterial activities were determined and pharmacokinetics and a clinical studies were performed on biapenem (L-627), a novel parenteral carbapenem antibiotic, in infections in children. The following results were obtained: 1. MICs of L-627 against clinical isolates were as follows: Among Gram-positive bacteria, MICs were 0.78 microgram/ml to > 100 micrograms/ml against 3 strains of methicillin-resistant Staphylococcus aureus (MRSA), and 0.10 microgram/ml to 0.39 microgram/ml against 8 strains of methicillin-sensitive S. aureus (MSSA), MICs against 5 of them were similar to those of imipenem (IPM), and MICs against 3 of them were slightly higher than those of IPM. MICs were < or = 0.025 microgram/ml to 0.39 microgram/ml against 7 strains of Streptococcus pneumoniae, and were similar to those of IPM, and lower than those of ceftazidime (CAZ) and piperacillin (PIPC). Among Gram-negative bacteria, MICs were 0.78 microgram/ml and 3.13 micrograms/ml against 2 strains of Haemophilus influenzae, and were similar to those of IPM. 2. Maximum plasma concentrations determined by the bioassay method after intravenous infusion of L-627 over 30 minutes at doses of 6.0 and 12.0 mg/kg, respectively, in 2 different pairs of 2 children each (total 4 cases) were observed upon completion of the treatment. Maximum concentrations at a dose of 6.0 mg/kg were 28.8 micrograms/ml and 24.6 micrograms/ml, and at a dose of 12.0 mg/kg were 65.4 micrograms/ml and 39.6 micrograms/ml, exhibiting a dose response. Plasma half lives in the beta phase were 0.97 and 1.20 hours at 6.0 mg/kg, and 0.72 and 0.94 hour at 12.0 mg/kg. Plasma concentrations determined by the HPLC method were lower than those determined by the bioassay. 3. Urinary excretion rates in the first 5.5 hours after the 6.0 mg/kg dose were 81.4 and 75.3%, and after the 12.0 mg/kg dose were 91.0 and 73.8%, and these values were higher than those obtained using HPLC. 4. Concentrations of L-627 in cerebrospinal fluid were determined in 2 cases of purulent meningitis. In one case, 30.3 mg/kg of L-627 was infused intravenously over 30 minutes and concentrations on days 1, 3, 7 and 14 observed at 60, 60, 45 and 45 minutes after respective dosages were 7.60, 1.30, 1.42 and 0.38 microgram/ml. Cerebrospinal fluid-plasma concentration ratio was determined on days 7 and 14 to be 5.5 and 1.2% respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

[Basic and clinical studies on cefditoren pivoxil in pediatric field].

Cefditoren pivoxil (CDTR-PI, ME1207) granules, a new oral cephem, was given to pediatric patients with infectious diseases to evaluate antibacterial activities against clinical isolates, pharmacokinetics, clinical efficacy and safety, and the following results were obtained. 1. In sensitivity test, 30 strains were used comprised of 5 species, isolated from the patients before administered with CDTR-PI. Against Staphylococcus aureus, MICs of 7 agents, cefditoren (CDTR), cefaclor, cefixime, cefteram, cefotiam, cefpodoxime and methicillin, were determined. Against other 4 species, MICs of the above 6 agents excluding methicillin were determined. Among Gram-positive cocci tested, the MICs of CDTR were 0.78 to 100 micrograms/ml or higher against S. aureus (16 strains), < or = 0.025 microgram/ml against Streptococcus pyogenes (5 strains), and 0.10 or 0.39 microgram/ml against Streptococcus pneumoniae (2 strains). These values were equal to or lower than those of conventional cephems and of methicillin. Among Gram-negative rods tested, the MICs of CDTR were < or = 0.025 microgram/ml against Haemophilus influenzae (3 strains), and 0.10 or 0.20 microgram/ml against Escherichia coli (4 strains). Also, these values were equal to or lower than those of conventional cephems. 2. When CDTR-PI granules was orally administered in a single dose of 3.0 mg/kg to 1 patient and that of 6.0 mg/kg to 2 patients 30 minutes after meal, plasma CDTR concentrations reached their maxima 4 hours after administration in the former patient and 1 or 2 hours after administration in the latter 2 patients, and the peak plasma concentrations were 1.91, 3.46 and 4.82 micrograms/ml with half-lives of 1.01, 0.81 and 0.88 hours and AUCs of 8.62, 9.89 and 13.52 micrograms.hr/ml, respectively. Dose-dependency was observed for the peak plasma concentrations and AUCs also tended to depend on dose excepting for the AUC in one 6.0 mg/kg patient. 3. The urinary concentrations in the above patients reached their peaks at 4 to 6 hours after administration in one 3.0 mg/kg patient and at 4 to 6 hours and 2 to 4 hours after administration in two 6.0 mg/kg patients, and the corresponding values were 126.0, 195.0 and 234.0 micrograms/ml, respectively. Recovery rates in the first 8 hours after administration were 18.2, 24.6 and 21.3%, respectively. 4. Of 53 patients with 13 diseases, CDTR-PI was clinically judged "excellent" in 32 (60.4%) and "good" in 21 (39.6%), showing excellent efficacy. 5. Bacteriologically, excellent results were obtained, i.e., 29 (96.7%) of 30 strains from 5 species were eradicated. 6. Side effects were observed in none of the 54 patients treated.(ABSTRACT TRUNCATED AT 400 WORDS)