Effects of a topical lotion containing aminophylline, caffeine, yohimbe, l-carnitine, and gotu kola on thigh circumference, skinfold thickness, and fat mass in sedentary females.

BACKGROUND AND OBJECTIVE: Topical aminophylline, caffeine, yohimbe, l-carnitine, and gotu kola (Centella asiatica) may aid in reducing body fat. Lipoxyderm™ contains these ingredients and was used to test if fat loss of the thigh, in conjunction with a low intensity exercise program and restricted calorie intake, was enhanced via the topical application of this lotion. METHODS: This was a double-blind, placebo-controlled, within-group study that investigated the effects of Lipoxyderm™ on thigh fat mass, circumference, and skinfold thickness. Seven participants underwent pre/post-exercise testing for weight, bilateral thigh circumference/skinfold thickness, and body composition/thigh fat mass assessment via dual-energy X-ray absorptiometry. Participants followed a hypocaloric diet, walked 150 minutes/wk, and were randomly assigned to apply a placebo to one leg and Lipoxyderm™ to their other leg for 28 days. Separate two-way mixed factorial repeated measures ANOVAs were used to compare the effects of Lipoxyderm™ to the placebo on thigh circumference, skinfold thickness, and fat mass. RESULTS: A significant time x group interaction was found for thigh circumference (F1,6  = 18.2, P = 0.005), skinfold thickness (F1,6  = 14.6, P = 0.009), and fat mass (F1,6  = 37.1, P = 0.001). CONCLUSIONS: A twice-daily topical application of Lipoxyderm™ for 28 days compared to a placebo combined with a walking program and a restricted caloric intake is more effective at reducing thigh circumference (1.2 vs 0.8 cm), thigh skinfold thickness (3.7 vs 2.0 mm), and thigh fat mass (100.0 g vs 57.3 g).

An interquartile relationship between polyherbal extract based lozenges linkus a phase IV comparative randomised control trial.

The aim of the study is to determine the efficacy of polyherbal linkus with the other pharmaceutical marketed syrup having Acefyllin Piperazine, Diphenhydramine group and Aminophylline Diphenhydramine group on the basis of interquartile ranges on children. It was open label multi centric randomize control trial. The study was conducted on different private schools of East and West Malir, Karachi Pakistan with the special approval from the school's honors .informed consent and assents were taking before the enrollment of the study subjects .The study enrolled participants were 147 who evaluate on cough. Participants were divided into 3 interventional group according to the treatment regimen .One group of participant received Linkus Syrup however the 2nd group received Acefyllin Piperazine and 3rd group received Aminophylline Diphenhydramine group. The frequency of the cough on linkus syrup was considered to be achieved on the basis of interquartile relationship and impact has been observed on child and parent sleep and found significant (p <0.01).Poly herbal Linkus Syrup has the significant impact on cough frequency and associated problem on children and parent's sleep with minimum side effects (p<0.01) however the pharmacological treatments are considered to be more unwanted effects on human subjects.

Aminophylline suppresses stress-induced visceral hypersensitivity and defecation in irritable bowel syndrome.

Pharmacological therapy for irritable bowel syndrome (IBS) has not been established. In order to find candidate drugs for IBS with diarrhea (IBS-D), we screened a compound library of drugs clinically used for their ability to prevent stress-induced defecation and visceral hypersensitivity in rats. We selected the bronchodilator aminophylline from this library. Using a specific inhibitor for each subtype of adenosine receptors (ARs) and phosphodiesterases (PDEs), we found that both A2BARs and PDE4 are probably mediated the inhibitory effect of aminophylline on wrap restraint stress (WRS)-induced defecation. Aminophylline suppressed maternal separation- and acetic acid administration-induced visceral hypersensitivity to colorectal distension (CRD), which was mediated by both A2AARs and A2BARs. We propose that aminophylline is a candidate drug for IBS-D because of its efficacy in both of stress-induced defecation and visceral hypersensitivity, as we observed here, and because it is clinically safe.

A Multicenter Clinical Study on Treating Post-Dural Puncture Headache with an Intravenous Injection of Aminophylline.

BACKGROUND: Post-dural puncture headache (PDPH) is the most common complication of lumbar puncture. Aminophylline has been reported to be effective in the prevention of PDPH in some clinical studies, but its efficacy for the treatment of PDPH has been unproven. OBJECTIVE: To evaluate the efficacy and safety of an intravenous (IV) injection of aminophylline on PDPH. STUDY DESIGN: The study was a multicenter, open-label study to assess the effectiveness and safety of aminophylline on PDPH. SETTING: The First Affiliated Hospital of Zhengzhou University, The Fifth Affiliated Hospital of Zhengzhou University, and Henan Province Hospital of Traditional Chinese Medicine. METHODS: Thirty-two PDPH patients received an IV injection of aminophylline. The primary and secondary endpoints were the degree of headache and the patient's overall response to the treatment, respectively. Treatment safety was evaluated based on the occurrence of adverse reactions. RESULTS: Thirty-one patients completed the study. Before the initial aminophylline administration, the visual analog scale (VAS) score was 7.72 ± 1.65. The VAS scores at 30 minutes, one hour, 8 hours, one day, and 2 days post-treatment were 4.84 ± 2.53, 3.53 ± 2.06, 2.38 ± 1.96, 1.44 ± 1.87, and 0.81 ± 1.79, respectively, and were statistically significantly different (P < 0.05) compared with those before treatment. More than 50% (17/32) of the patients reported that they were "very much improved" or "much improved" 30 minutes after the initial treatment, increasing to 93.8% (30/32) at 2 days post-treatment. One patient experienced mild allergic reaction after treatment. LIMITATIONS: Although this study had the largest sample size among current studies on treating PDPH with theophylline drugs, the sample size was still relatively small and the method employed was not compared with a placebo or other current clinical treatments for PDPH. CONCLUSION: An IV injection of aminophylline may be an effective and safe early-stage treatment for PDPH.

Safety considerations for patients with epilepsy taking antiepileptic drugs alongside caffeine or other methylxanthine derivatives.

INTRODUCTION: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy. However, ∼ 30% of patients do not remain seizure free. It is possible that methylxanthine derivatives (e.g., caffeine and theophylline) may partially account for this outcome. AREAS COVERED: Data on the convulsive activity of methylxanthines are reviewed. The negative impact of caffeine and theophylline (or aminophylline) on the protective activity of classic and newer AEDs is also considered. Case report studies indicate that ingestion of caffeine may increase seizure frequency, which returns to baseline when the consumption of coffee or caffeine-rich drinks is terminated. However, the existing data also provide clinical evidence that caffeine may not be a trigger for precipitation of seizure activity and this discrepancy is evaluated. EXPERT OPINION: Experimental data indicate that caffeine and aminophylline both significantly reduce the anticonvulsant activity of a number of AEDs. Clinical data are controversial. Patients with epilepsy should be advised not to take methylxanthine-containing medications. Caffeine consumption, especially accidental and in huge quantities, should be avoided in patients with epilepsy.

Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms.

OBJECTIVE: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied. MATERIALS AND METHODS: Three modified-release formulations of aminophylline consisted of Carbopol® 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350 mg tablets, Srbolek, Serbia (R-I) and Phyllocontin(®) 350, tablets Purdue Frederic, Canada (R-II). RESULTS: Calculated release rate constants and the ƒ2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher Tmax, was found in the rabbits, dosed with F-II (12.00 h), F-III (10.50 h), and R-II (15.00 h) formulation. The highest Cmax (9.22 mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58 mg/L) and R-II (4.18 mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L). DISCUSSION AND CONCLUSION: The results demonstrated a good correlation of Level A (r(2) = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.

Novel chronotherapeutic rectal aminophylline delivery system for therapy of asthma.

The aim of this study was to develop a new chronotherapeutic pharmaceutical preparation as a sustained-release suppository for prevention and therapeutic use against bronchial asthma in the early morning. Sustained-release hollow-type (SR-HT) suppositories using sodium alginate (Alg-Na), sodium polyacrylate (PANa) or polyacrylate-PANa co-polymer (PA-PANa) as gelling polymers (gel agent) were prepared and pharmaceutical characteristics of these suppositories were investigated. Type A SR-HT suppositories comprised a suppository shell prepared with oleaginous base and containing aminophylline only or aminophylline with Alg-Na or PANa in the cavity (hollow space). Type B SR-HT suppositories comprised a suppository shell prepared with oleaginous base and gel agent (30%), with aminophylline in the hollow space. In drug-release studies, the acrylate polymer-containing suppositories showed linearity of delayed release rate, providing significantly decreased the highest concentration of theophylline in plasma (C(max)) and delayed the time required to reach C(max) (t(max)) and the mean residence time (MRT) after rectal administrated in rabbits. In particular, suppositories containing PA-PANa maintained significantly higher theophylline concentrations than control suppositories at 12h after rectal administration. Furthermore, histopathological examination indicated that these suppositories using acrylate polymers did not result in rectal lesions. The SR-HT suppository, particularly using PA-PANa as a gel agent, may thus be useful against nocturnal symptoms of asthma. In this study, we confirmed new formulation of sustained-release suppository for chronotherapy of theophylline using oily base material in combination with polymer such as PA-PANa. The hollow-type suppository containing oleaginous base and hydrophilic polymer in the shell could be useful device for rectal administration of various drugs with prolongation of plasma concentration.

Vehicle and enhancer effects on human skin penetration of aminophylline from cream formulations: evaluation in vivo.

The effects of four essential oils (rosemary, ylang, lilacin, and peppermint oils), and three plant oils (jojoba oil, corn germ oil, and olive oil) on the permeation of aminophylline were studied using human skin. The permeation effects of these oils were compared with those of three chemical penetration enhancers. Although all oils enhanced the permeation of aminophylline, their effects were less than that of ethanol. Jojoba oil was found to be the most active, causing about a 32% peak height decrease of N-H bending absorbances in comparison with the control, while peppermint, lilacin, rosemary, and ylang oils caused 28%, 24%, 18%, and 12% peak height decreases, respectively. Microemulsions containing 10% jojoba oil and 30% corn germ oil were found to be superior vehicles for the percutaneous absorption of aminophylline. Comparision with results obtained from high-performance liquid chromatography shows good agreement.

[Study on evaluation index of acupoint transdermal administration--drug delivery coefficient].

OBJECTIVE: To investigate the correlation of skin electric resistance changes with the blood drug content in acupoint transdermal administration, and to establish an new evaluation index for drug delivery efficiency through acupoints. METHODS: Twenty-four rabbits were randomly divided into an observation group and a control group. In the observation group, aminophylline was administrated through "Feishu" (BL 13), "Geshu" (BL 17) and "Danzhong" (CV 17) which are commonly used for treatment of bronchial asthma, and the control group through sham-points on the back. The skin resistance and plasma aminophylline content were determined after application of aminophylline to the points, and their changes with time were observed. The ratio of Css/Rss at stability was defined as delivery coefficient (DC) which reflects the efficiency of delivering drug at acupoints and sham acupoints. RESULTS: Both the plasma aminophylline and the skin resistance value tended to steady about 6-8 h after application of aminophyiophylline. The DC in the acupoints was higher than that in the sham-acupoints (P < 0.01). And there was significant difference as DC of the "Feishu"was significant difference (BL 13) and "Danzhongas DC of the "Feish" (BLCV 17) compared with that of "Geshu" (BL 17) (P < 0.01). CONCLUSION: The bigger the DC is, the higher the efficiency of drug delivery is; the efficiency of drug delivery through acupoints is higher than that through sham-acupoints.

[Hemodynamic effects of aminophylline and nifedipine in patients with high altitude pulmonary edema].

AIM: To evaluate the hemodynamic effects of aminophylline and nifedipine in patients with HAPE. METHODS: 10 patients with HAPE undergone Swan-Ganz catheter. The parameters of hemodynamics and arterial blood gases in HAPE were measured before and after administration of nifedipine 20 mg sublingually and aminophylline 0.25 g intravenously respectively. RESULTS: After administering 0.25 g aminophylline the mPAP and PVR significantly decreased, the cardiac output and the level of PaO2, SaO2 increased obviously, the mSAP, HR did not change so much. After using 20 mg nifedipine, the mPAP, PVR and mSAP also decreased, while the cardiac output, HR and the level of PaO2, SaO2 did not show any changes. CONCLUSION: Both of aminophylline and nifedipine can attenuate pulmonary hypertension in patients with HAPE, but the effect of aminophylline was better than the effect of nifedipine.

Effect of some convulsants on the protective activity of loreclezole and its combinations with valproate or clonazepam in amygdala-kindled rats.

Loreclezole (5 mg/kg) exerted a significant protective action in amygdala-kindled rats, reducing both seizure and afterdischarge durations. The combinations of loreclezole (2.5 mg/kg) with valproate, clonazepam, or carbamazepine (applied at their subprotective doses) also exhibited antiseizure effect in this test. However, only two first combinations occurred to be of pharmacodynamic nature. Among several chemoconvulsants, bicuculline, N-methyl-D-aspartic acid and BAY k-8644 (the opener of L-type calcium channels) reversed the protective activity of loreclezole alone and its combination with valproate. On the other hand, bicuculline, aminophylline and BAY k-8644 inhibited the anticonvulsive action of loreclezole combined with clonazepam. The results support the hypothesis that the protective activity of loreclezole and its combinations with other antiepileptics may involve potentiation of GABAergic neurotransmission and blockade of L-type of calcium channels.

Dose response of intrathecal adenosine in experimental pain and allodynia.

BACKGROUND: Intrathecal adenosine reduces areas of mechanical hypersensitivity and provides analgesia in patients with neuropathic pain. Adenosine also causes side effects, yet its dose response for either efficacy or side effects has not been examined in double blind studies. We studied two doses of intrathecal adenosine in humans with experimental hypersensitivity and the ability of the adenosine receptor antagonist, aminophylline, to reverse adenosine's effects. METHODS: Following Internal Review Board approval and written informed consent, 35 volunteers were studied. Five volunteers were studied to confirm the stability of a new method of inducing hypersensitivity with capsaicin. The remaining 30 volunteers received, in a randomized, double-blind manner, saline, or adenosine, 0.5 or 2.0 mg, by intrathecal injection 40 min after areas of allodynia and hyperalgesia were established from capsaicin. Two hr later, volunteers were randomized to receive intravenous saline or aminophylline, 5 mg/kg. RESULTS: Topical capsaicin with intermittent heating resulted in stable areas of allodynia and hyperalgesia. Intrathecal adenosine, but not saline, reduced areas of allodynia and hyperalgesia from capsaicin, with no differences between doses. Side effects occurred in 1, 2, and 6 volunteers receiving saline, 0.5 mg and 2.0 mg adenosine, respectively. Aminophylline failed to reverse adenosine's effects. CONCLUSIONS: There is no difference in efficacy to experimental hypersensitivity between the largest approved dose of intrathecal adenosine and a dose 25% this size, but side effects are more common with the larger dose. Failure of aminophylline to reverse adenosine's effects could reflect inadequate concentrations at receptors in the spinal cord after intravenous injection.

Three-dimensional nonfluoroscopic mapping and ablation of inappropriate sinus tachycardia. Procedural strategies and long-term outcome.

OBJECTIVES: We conducted this study to assess long-term results of three-dimensional (3-D) mapping-guided radiofrequency ablation (RFA) of inappropriate sinus tachycardia (IST). Change in activation after the administration of esmolol was also assessed and compared to the shift documented with successful sinus node (SN) modification. BACKGROUND: The long-term results after RFA of IST have been reported to vary between 27% and 66%. METHODS: Thirty-nine patients (35 women, mean age 31 +/- 9 years) with debilitating IST were included in the study. The area around the earliest site of activation recorded using the 3-D mapping system was targeted for ablation. The shift in the earliest activation site after administration of esmolol was compared with the shift after RFA. RESULTS: The heart rate at rest and in drug-free state ranged between 95 and 125 beats/min (mean 99 +/- 14 beats/min). Sinus node was successfully modified in all patients. Following ablation, the mean heart rate dropped to 72 +/- 8 beats/min, p < 0.01. The extent of the 3-D shift in caudal activation along the crista terminalis was more pronounced after RFA than during esmolol administration (23 +/- 11 mm vs. 7 +/- 5 mm, respectively, p < 0.05). No patient required pacemaker implantation after a mean follow-up time of 32 +/- 9 months; 21% of patients experienced recurrence of IST and were successfully re-ablated. CONCLUSIONS: Three-dimensional electroanatomical mapping seems to facilitate and improve the ablation results of IST. The difference in caudal shift seen after esmolol administration and following SN modification suggests that adrenergic hypersensitivity is not the only mechanism responsible for the inappropriate behavior of the SN.

Topical vasoactive cream in the treatment of erectile failure: a prospective, randomized placebo-controlled trial.

OBJECTIVE: To repeat a previous study on the use of a topical treatment for erectile failure using a vasoactive cream. PATIENTS AND METHODS: Fourteen patients with erectile failure who had previously responded to intracorporeal injection therapy were enrolled in a randomized placebo-controlled trial. They were given two topical applications, comprising either a cream containing aminophylline, isosorbide dinitrate and co-dergocrine mesylate, or a placebo cream of similar appearance containing no pharmacologically active ingredients. Each patient received 16 applications, eight of the active cream and eight placebo. The creams were applied alternatively on successive occasions and the results recorded. RESULTS: The active cream, applied on 77 occasions, resulted in three good and 13 partial erections. The placebo cream, applied on 76 occasions, yielded four good and 13 partial erections. CONCLUSIONS: We were unable to reproduce the successful results reported by others; in the present study the active cream performed no better than placebo.

Cellulite treatment: a myth or reality: a prospective randomized, controlled trial of two therapies, endermologie and aminophylline cream.

Cellulite is a common phenomenon that particularly affects the thighs and buttocks of women. Little scientific evidence exists to support any of the many advertised treatments for it. A total of 52 of 69 women, who were divided into three groups, completed a 12-week, randomized, controlled trial in which the effectiveness of two different treatments for cellulite was assessed. The patients acted as their own controls. The treatments investigated were twice-daily application of aminophylline cream and twice-weekly treatment with Endermologie ES1. Group 1 (double blind) received aminophylline to one thigh/buttock and a placebo cream to the other. Group 2 (singly blind) received Endermologie to one thigh/buttock. Group 3 received Endermologie to both sides and used the same cream regimen as group 1. Results were assessed subjectively by the patient and by clinical examination and photographic assessment by the surgeon (before and after the trial). Morphologic assessment included body mass index, thigh girth at two points, and thigh fat depth measurement by ultrasound. No statistical difference existed in measurements between legs for any of the treatment groups (paired t test, p > 0.4). The best subjective assessment, by the patients themselves, revealed that only 3 of 35 aminophylline-treated legs and 10 of 35 Endermologie-treated legs had their cellulite appearance improved. The authors do not believe that either of these two treatments is effective in improving the appearance of cellulite.

Adenosine mediates spinal norepinephrine-produced antinociception as revealed by nociceptive discharges in parafascicular neurons in rats.

The effects of intrathecal pretreatment with aminophylline on intrathecal norepinephrine-produced or serotonin-produced suppression of noxiously evoked discharges in thalamic parafascicular neurons were investigated in 35 urethane-anesthetized rats. The results showed that: (1) both intrathecal norepinephrine (15 nmol) or serotonin (20 nmol) produced significant suppression of noxiously evoked discharges in parafascicular neurons; (2) intrathecal aminophylline (120 nmol) blocked the norepinephrine-produced suppression of noxiously evoked discharges, while the same dose of aminophylline exhibited no significant effect on the serotonin-produced suppression of these discharges in parafascicular neurons. The results suggest that spinal norepinephrine-produced, but not serotonin-produced, antinociceptive effects may be mediated by adenosine as one of successive chemical links in the spinal dorsal horn circuitry.

[Low-concentration nitrous oxide inhalation in the treatment of high-altitude pulmonary edema].

OBJECTIVE: To investigate the therapeutic effect of low-concentration of nitroic oxide (NO) inhalation in high-altitude pulmonary edema. METHOD: Sixty-five male patients with high-altitude pulmonary edema were randomized into three groups. Patients in the conventional therapy group received oxygen, intravenous furosemide, aminophylline and dexamethasone; patients in the nifedipine group received oral nifedipine (10 mg, tid) in addition to conventional therapy; and patients in the NO group received NO (10 ppm) inhalation for 30 min, in addition to oral nifedipine. The time for which pulmonary rales on auscultation and shadows on chest radiograph lasted, and the course of disease, were compared. RESULT: In the NO group, pulmonary rales disappeared in 0.4 +/- 0.3 d, shadows on chest radiograph disappeared in 0.6 +/- 0.2 d, and the course of disease was 1.8 +/- 0.7 d, all of which were significantly different from those of the nifedipine group (2.4 +/- 1.4 d, 4.1 +/- 1.7 d, 6.8 +/- 1.8 d, respectively) and the conventional therapy group (3.7 +/- 1.2 d, 5.5 +/- 1.8 d, 9.6 +/- 3.1 d, respectively). CONCLUSION: Low-concentration NO inhalation on the basis of conventional and nifedipine therapies was very effective in the treatment of high-altitude pulmonary edema, which deserves further and larger scale investigation.

Effects of theophylline on renal function in premature infants.

Xanthines are frequently being used in the management of premature babies. Studies in adult subjects have demonstrated a diuretic effect of aminophylline due to the inhibition of solute reabsorption in various segments of the nephron. We evaluated the effects of aminophylline on the developing kidney. Nineteen premature infants, with a mean +/- SD gestational age of 31.1 +/- 2.8 weeks and mean birth weight of 1481 +/- 454 g were studied at mean age of 4.5 +/- 4.0 days before and after a 20-minute loading infusion of 6 mg/kg aminophylline, followed by maintenance therapy at a dose of 2 mg/kg every 12 hours. A marked diuresis occurred immediately after the loading dose, the ratio of urinary output to water intake increased from 0.58 +/- 0.36 to 1.19 +/- 0.65. Concomitantly, the fractional excretion of sodium increased from 2.7 +/- 2.6% to 5.7 +/- 4.4% and that of potassium rose from 21 +/- 19% to 31 +/- 21%. Urinary calcium and uric acid excretion were also enhanced: calcium to creatinine ratio rose from 0.31 +/- 0.29 to 0.60 +/- 0.54 and uric acid to creatinine ratio increased from 2.5 +/- 1.5 to 3.8 +/- 2.0. Tubular reabsorption of phosphorus (TRP) was not affected. Most of the effects were no longer evident after 24 hours, despite continuing aminophylline maintenance therapy. In premature infants the aminophylline loading dose, but not maintenance therapy, affected renal functions. Because heart rate, blood pressure, and creatinine clearance did not change, it appears that aminophylline acts directly on tubular reabsorptive functions.