Combined therapy for resistant vitiligo lesions: NB-UVB, microneedling, and topical latanoprost, showed no enhanced efficacy compared to topical latanoprost and NB-UVB.

Vitiligo is depigmenting disorder of the skin and mucous membranes but despite various therapeutic options, complete and satisfactory treatment of vitiligo still remains a challenge. Therapeutic success also varies depending on the localization of lesions; hands and bony prominents are considered to be resistant to treatment. We investigated feasibility of treating resistant bilateral symmetrical vitiligo vulgaris and acrofacialis lesions with combination of narrowband UVB and topical prostaglandins (0.005% latanoprost solution) with or without Dermaroller 0.5 mm needle length-assisted microneedling. Frequency of repigmentation onset was generally low (37.8%) and pronounced repigmentation was infrequently seen (26-50% repigmentation in 20.8%, and >50% repigmentation in only 8.8% of repigmenting lesions). Our study, however, showed that latanoprost can be used in combination with NB-UVB phototherapy to induce repigmentation in some vitiligo lesions in resistant-to-treatment location, while addition of skin microneedling seems not to improve the treatment outcome and possibly needs modification.

A pilot comparative study of topical latanoprost and tacrolimus in combination with narrow-band ultraviolet B phototherapy and microneedling for the treatment of nonsegmental vitiligo.

Prostaglandins and their analogues are beneficial as topical agents in vitiligo treatment, yet neither of the previous study addressed their comparative efficiency with conventional topical agents used in vitiligo treatment. In this pilot (24 patients) left-right comparative study we addressed efficiency of prostaglandin F2α analogue latanoprost versus tacrolimus when combined with narrow-band ultraviolet B and microneedling in repigmentation of nonsegmental vitiligo lesions. Our results confirm potency of prostaglandins, in particular, that of latanoprost, in inducing repigmentation, with the efficiency being at least comparable to that of tacrolimus, while contribution of microneedling remains unclear. In summary, results of our study provide further evidences for justified use of prostaglandins, in particular, latanoprost, in vitiligo treatment. In turn, this warrants future studies on the topic aiming to conclusively introduce prostaglandin-based formulations as conventional agents for vitiligo management.

Promising alternative clinical uses of prostaglandin F2α analogs: beyond the eyelashes.

Prostaglandin F2α analogs, commonly prescribed for glaucoma treatment, have been shown to induce side effects such as cutaneous hypertrichosis and hyperpigmentation. Therefore, these medications have theoretic applications in the treatment of alopecia and disorders of hypopigmentation. We reviewed the literature to find original studies assessing the use of prostaglandin F2α analogs in these settings. Studies and reports were analyzed in regards to androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring. Based on the results of these studies, and consideration of pathophysiologic mechanism, the most promising applications for prostaglandin F2α analogs include androgenic alopecia, chemotherapy-induced alopecia, and alopecia areata concurrently treated with corticosteroids.

[ProVens® in the Therapy of Glaucoma and Ocular Hypertension]. / ProVens® v lécbe glaukomu a ocní hypertenze.

OBJECTIVE: To assess the effect of the ProVens® dietary supplement administration on intraocular pressure in patients with glaucoma and ocular hypertension. MATERIAL AND METHODS: The patients included in the trial were given the ProVens® dietary supplement once daily. One ProVens® tablet contains: 50 mg of maritime pine bark extract, 100 mg of green tea extract, and 3 mg of blueberry extract. The main ProVens® components are proanthocyanins from the bark of the maritime pine tree Pinus pinaster, polyphenols from green tea, and anthocyanins from blueberries. The total number of patients included in the trial was 46. Out of these, 35 patients were monitored for asymptomatic ocular hypertension and 11 patients for open-angle glaucoma treated with prostaglandin analogs. Intraocular pressure was measured by applanation tonometry in the beginning of the trial, after one month, and after three months of their inclusion in the trial, always at the same time of the day. RESULTS: In the group of patients with ocular hypertension, there was a statistically significant reduction in the intraocular pressure from the baseline values of 24.2 ± 2.1 mm Hg to 20.9 ± 2.5 mm Hg within the period of three months (p < 0.0001). In the group of patients with open-angle glaucoma, there was a statistically significant reduction of the intraocular pressure from the baseline values of 18.4 ± 3.2 mm Hg to 17.0 ± 3.1 mm Hg within the period of three months since the beginning of administration of the product (p = 0.022). When comparing both groups, we observed a significantly higher reduction in intraocular pressure (p = 0.0001) in the group of patients with ocular hypertension. In the whole group, no adverse effects were reported during the intake of this dietary supplement. CONCLUSION: Intake of the ProVens® dietary supplement containing proanthocyanins from the bark of the maritime pine tree Pinus pinaster together with a mixture of herbal antioxidants appears to be one of the methods of how to improve the control of intraocular pressure, particularly in patients with ocular hypertension. KEY WORDS: glaucoma, ocular hypertension, ProVens®, proanthocyanins, antioxidants, maritime pine bark extract.

The long-term outcomes of four alternative treatment strategies for primary open-angle glaucoma.

PURPOSE: To evaluate the long-term effects and costs of four treatment strategies for primary open-angle glaucoma compared to usual care. METHODS: Cost-effectiveness analyses with a lifelong horizon were made from a societal perspective. Data were generated with a patient-level model based on discrete event simulation. The model structure and parameter estimates were based on literature, particularly clinical studies on the natural course of glaucoma and the effect of treatment. We simulated heterogeneous cohorts of 3000 patients and explored the impact of uncertainty with sensitivity analyses. RESULTS: The incremental cost-effectiveness ratio (ICER) of initial treatment with a prostaglandin analogue compared with a ß-blocker was €12.931 per quality-adjusted life year (QALY) gained. A low initial target pressure (15 mmHg) resulted in 0.115 QALYs gained and €1550 saved compared to a gradual decrease from 21 to 15 mmHg upon progression. Visual field (VF) measurements every 6 rather than 12 months lead to health gains at increased costs (ICER €173,486 per QALY gained), whereas measurements every 24 months lead to health losses at reduced costs (ICER €21,516 per QALY lost). All treatment strategies were dominant over 'withholding treatment'. CONCLUSIONS: From a cost-effectiveness point of view, it seems advantageous to aim for a low intraocular pressure in all glaucoma patients. The feasibility of this strategy should therefore be investigated. Additionally, the cost-effectiveness outcomes of initiating monotherapy with a prostaglandin analogue and reducing the frequency of VF testing may be acceptable.

A model-based meta-analysis of the effect of latanoprost chronotherapy on the circadian intraocular pressure of patients with glaucoma or ocular hypertension.

Several reports have demonstrated that the efficacy of latanoprost is influenced by the time of dosing. This model-based meta-analysis validates previous findings that evening dosing is superior to morning dosing and predicts the optimal time for dosing, based on the quantitative assessment of baseline and latanoprost-treated 24-h circadian intraocular pressure (IOP) curves. The results confirm the importance of the time of dosing as a factor that influences the extent of reduction in IOP and underline the need to take this factor into consideration in the design of glaucoma trials and therapy.

Alternative low doses and routes of administering a prostaglandin F2alpha analogue to induce luteolysis in Nelore cows.

The present study was conducted in order to verify the efficacy of lower doses and alternative routes of a prostaglandin F2alpha analogue, luprostiol (PGF), for the induction of luteolysis and the precipitation of estrus in nonlactating Nelore cows (Bos taurus indicus). A conventional dose (15 mg) of PGF was compared to doses lower than the conventional dose, which ranges from 10 to 50%, that were administered intramuscularly (IM), intravulvosubmucosally (IVSM), or in the Bai-hui acupuncture site located within the lumbosacral area. The cows were administered PGF 8 day after estrus in the presence of a corpus luteum, and randomly assigned to the following groups: G1 (positive control), 15 mg, IM (n = 23); G2, 7.5 mg, IM (n = 23); G3, 3.75 mg, IM (n = 24); G4, 7.5 mg, IVSM (n = 25); G5, 3.75 mg, Bai-hui acupoint (n = 24); and G6, 1.5 mg, Bai-hui acupoint (n = 25). The results indicated that 50% of a conventional dose of PGF (7.5 mg) resulted in a complete luteal regression (plasma progesterone <1 ng/ml) at Hour 48, and hastened estrus, regardless of whether or not PGF was administered IM or IVSM. Comparatively, 10 or 25% of the conventional dose, even when administered to the Bai-hui acupoint, resulted in an initial reduction in the concentration of progesterone at Hour 24, followed by an increase observed at Hour 48. In conclusion, 25% of a conventional PGF dose administered via the Bai-hui acupoint proved inadequate to induce a complete luteal regression, whereas 50% of a conventional dose administered IM or IVSM was found to be the minimal dose required to induce effectively a complete luteal regression, and to precipitate the onset of estrus in nonlactating Nelore cows.

Alternative low doses and routes of administering a prostaglandin F2alpha analogue to induce luteolysis in Nelore cows

The present study was conducted in order to verify the efficacy of lower doses and alternative routes of a prostaglandin F2 alpha analogue, luprostiol (PGF), for the induction of luteolysis and the precipitation of estrus in nonlactating Nelore cows (Bos taurus indicus). A conventional dose (15 mg) of PGF was compared to doses lower than the conventional dose, which ranges from 10 to 50%, that were administered intramuscularly (IM), intravulvosubmucosally (IVSM), or in the Bai-hui acupuncture site located within the lumbosacral area. The cows were administered PGF 8 day after estrus in the presence of a corpus luteum, and randomly assigned to the following groups: G1 (positive control), 15 mg, IM (n = 23); G2, 7.5 mg, IM (n = 23); G3, 3.75 mg, IM (n = 24); G4, 7.5 mg, IVSM (n = 25); G5, 3.75 mg, Bai-hui acupoint (n = 24); and G6, 1.5 mg, Bai-hui acupoint (n = 25). The results indicated that 50% of a conventional dose of PGF (7.5 mg) resulted in a complete luteal regression (plasma progesterone <1 ng/ml) at Hour 48, and hastened estrus, regardless of whether or not PGF was administered IM or IVSM. Comparatively, 10 or 25% of the conventional dose, even when administered to the Bai-hui acupoint, resulted in an initial reduction in the concentration of progesterone at Hour 24, followed by an increase observed at Hour 48. In conclusion, 25% of a conventional PGF dose administered via the Bai-hui acupoint proved inadequate to induce a complete luteal regression, whereas 50% of a conventional dose administered IM or IVSM was found to be the minimal dose required to induce effectively a complete luteal regression, and to precipitate the onset of estrus in nonlactating Nelore cows.

The influence of diclofenac ophthalmic solution on the intraocular pressure-lowering effect of topical 0.5% timolol and 0.005% latanoprost in primary open-angle glaucoma patients.

The aim of this randomized, prospective, masked clinical study has been to verify the influence of a non-steroidal anti-inflammatory drug ophthalmic solution on intraocular pressure reduction induced by 0.5% timolol and 0.005% latanoprost eyedrops in patients affected by primary open-angle glaucoma. Thirty-two glaucomatous patients, compensated with 0.5% timolol, were randomized into two study groups (A and B). Timolol was continued for the first 2 weeks in all subjects. On the 15th day, in both groups timolol was replaced by latanoprost, and this regimen lasted up to the end of the follow-up (8 weeks). At the beginning of the 2nd week of the study, group A additionally started a 5-week therapy with topical 0.1% diclofenac; during the same period, group B received placebo eyedrops with identical modalities. Intraocular pressure was recorded at 7-day intervals during the first 7 weeks and at the 10th week. Non-steroidal anti-inflammatory drug and placebo did not modify the effect of timolol on intraocular pressure. In both groups, latanoprost induced a significant decrease in intraocular pressure. Diclofenac-treated patients exhibited a marked fall in intraocular pressure (p<0.01), whereas in placebo-treated patients, this diminution was less noticeable (p<0.05). After diclofenac withdrawal, in group A intraocular pressure significantly increased (p<0.01), remaining approximately at the same level up to the end of the study. In group B, at the same checks no significant variations in intraocular pressure occurred. In primary open-angle glaucoma patients, diclofenac significantly enhances the hypotensive effect of latanoprost, without influence on timolol efficacy. Because non-steroidal anti-inflammatory drugs are widely employed in medical practice, supplementary ophthalmologic checks should be scheduled during the co-administration of these compounds and prostaglandin analogues.

[Circadian rhythm variations of intraocular pressure and therapeutic decisions: interpretation of clinical trial results based on a statistical model]. / Variations nycthémérales de la pression intraoculaire et décisions thérapeutiques: Interprétation des résultats d'essais cliniques à partir d'un modèle statistique.

Therapeutic decisions (treatment initiation, continuation, change, combination, etc.) based on intraocular pressure (IOP) monitoring require knowledge of both circadian IOP fluctuations and the pharmacological circadian rhythm of the active ingredients. A simple model was applied to data from two clinical trials to estimate the consequences of circadian IOP fluctuations on (1) ocular hypertension diagnosis, (2) therapeutic adjustments, and (3) the daily cumulative effect of marginally low therapeutic differences. A grid for clinical interpretation of the average IOP differences is presented. The probability of an IOP that exceeds the target value for the diagnosis or therapy varied to a large extent throughout the day. IOP was higher in the morning than in the evening. The IOP variance (measured by standard deviation) was an important factor in decision-making, regardless of the IOP value itself. Regular IOP monitoring over the entire day allowed minimization of the time spent above a target value. IOP differences that seemed low when expressed in average values in therapeutic trials could have clinically significant consequences in the practitioner's decisions. The data presented suggest that ocular hypertension diagnosis and therapeutic decisions should be made early in the morning, at least for most patients. In any case, the time of the measurement should be considered in the therapeutic approach.

Short-term effect of latanoprost and timolol eye drops on tear fluid and the ocular surface in patients with primary open-angle glaucoma and ocular hypertension.

PURPOSE: To investigate and compare the short term effects of topical latanoprost and timolol on the tear fluid and ocular surface condition in patients with bilateral primary open angle glaucoma or ocular hypertension. METHODS: Thirty-seven patients were included in this randomized, double-masked, parallel group study. Patients received either latanoprost 0.005% (n= 18) or timolol 0.5% (n= 19) instilled once daily in the morning for a treatment period of 27 days. Routine ophthalmic examinations, including intraocular pressure measurement, as well as tests to evaluate tear fluid and the ocular surface were performed. RESULTS: After one drop of medication, tear secretion was significantly reduced by timolol, but not by latanoprost. At the end of the study the break-up time (BUT) was significantly decreased in the timolol group but not in the latanoprost group. The BUT still remained in the normal range in both groups, although it is important to note that timolol was administered at half the clinical dose. Both latanoprost and timolol tended to increase Rose-Bengal staining of the cornea and conjunctiva after one month of treatment but no statistically significant difference was found between the groups. Corneal sensitivity was within the normal range for all patients during the study. CONCLUSION: Regarding ocular surface effects, no clinically important differences between latanoprost and timolol were observed as all the effects remained in the normal range.

The ocular effects of prostaglandins and the therapeutic potential of a new PGF2 alpha analog, PhXA41 (latanoprost), for glaucoma management.

In the early days of prostaglandin (PG) research, the infusion of large PG doses into rabbit eyes already traumatized by cannulation, led to the conclusion that PGs have a profound ocular hypertensive effect that is associated with a breakdown of the blood-aqueous barrier. In contrast, repeated topical application of PGs to nontraumatized eyes of several species other than rabbits has later been shown to yield a maintained ocular hypotensive effect, without barrier breakdown. Due to its excellent pharmacokinetic properties, the isopropyl ester form of PGF2 alpha (PGF2 alpha-IE) is a much more potent ocular hypotensive agent and appeared to be better suited for the management of glaucoma, than PGF2 alpha itself or any currently used glaucoma drug. However, even this prodrug caused clinically unacceptable foreign-body sensation and conjunctival hyperemia, which could be reduced, or eliminated, only by some modifications of the omega chain of PGF2 alpha-IE. One such analog, PhXA41, maintained highly significant IOP reduction in glaucoma patients even with once-daily application at the remarkably low concentration of 0.006%. Because PhXA41 reaches intraocular tissues and the systemic circulation in its de-esterified free-acid form, which is a good substrate for the PG transport system, it retains the most important pharmacokinetic advantages of topically applied PGF2 alpha-IE. However, its greatly reduced side effects give PhXA41 a clear therapeutic advantage over PGF2 alpha-IE, making it an effective new drug candidate for the long-term medical management of glaucoma.

Cervical dilatation in late first trimester termination by prostaglandin, hylase and isogel.

Pre-operative dilatation of the cervix was attempted in 223 cases prior to vacuum aspiration in patients seeking late first trimester termination beyond ten weeks. 15 Me PGF2a was used in the form of vaginal suppositories, intramuscular and intracervical injections. Dilatation of cervix of 10 mm or more was achieved within 4 hours in 86% cases with intra-cervical injections. Gastro-intestinal disturbances caused by intra-muscular injections could be avoided by intra-cervical injections, as the amount of prostaglandin required was only 100 ugm, but the success rate was significantly lower. The success with multiple dose suppositories was 80%. There was no significant difference in the success with 1.5 mgm or 1.0 mgm dosage, but the side effects were significantly higher with 1.5 mgm suppositories. Intra-cervical Hylase did not dilate the cervix but successfully softened it within 5 minutes to make metallic dilatation simple. The hygroscopic Isogel tents achieved dilatation of 10 mm or more in 73% of the patients in 12 hours. The tents as well as intra-cervical prostaglandin injection had the disadvantage of requiring an additional theatre procedure prior to suction curettage.

PIP: Preoperative dilatation of the cervix was attempted in 223 cases prior to vacuum aspiration in patients seeking late first trimester termination beyond 10 weeks. 15 Me PGF2alpha was used in the form of vaginal suppositiories, intramuscular and intracervical injections. Dilatation of cervix of 10 mm or more was achieved within 4 hours in 86% cases with intracervical injections. Gastrointestinal disturbances caused by intramuscular injections could be avoided by intracervical injections, as the amount of (PG) prostaglandin required was only 100 ugm, but the success rate was significantly lower. The success with multiple dose suppositories was 80%. There was no significant difference in the success with 1.5 mgm or 1.0 mgm dosage, but the side effects were significantly higher with 1.5 mgm suppositories. Intracervical Hylase did not dilate the cervix but successfully softened it within 5 minutes to make metallic dilatation simple. The hygroscopic Isogel tents achieved dilatation of 10 mm or more in 73% of the patients in 12 hours. The tents as well as intracervical PG injection had the disadvantage of requiring an additional theater procedure prior to suction curettage.

[Steroid and nonsteroid postcoital contraceptives]. / Steroidnye i nesteroidnye kontratseptivy postkoital'nogo deistviia.

It has been shown experimentally that a combined use of estrogen-norsteroids prostaglandins and neurotropic substances during preimplantation period produces the most potent contraceptive effect. Analysis of the action mode of combined small doses of steroids, prostaglandins and neurotropic drugs suggests that the contraceptive action is underlain by the inhibitory effect on incretion produced by the luteinizing hormone, this effect being in its turn a reason for variation in the amount and condition of the developing fetuses.

Comparison of the lytic effects of four prostaglandin analogues in the chacma baboon (Papio ursinus ursinus).

Six healthy, cycling female chacma baboons (Papio ursinus ursinus) were used to determine the luteolytic effects of four prostaglandin analogues. The compounds were administered according to a study design which made provision for adequate controls. Five to seven days following ovulation, venous blood was collected and the baboon given a single intramuscular injection of a compound at a recommended dose. Blood was then collected serially every 3 h for three samples and again at 24, 48, and 72 h to determine the continued effect of the prostaglandin analogues on corpus luteum production of progesterone. It was found that PGF2alpha-1,15-lactone, 11alpha(15S)-17-phenyl-18,19,20-trinor-ent-PGE2 methyl ester and 17-phenyl-18,19,20-trinor-PGF2alpha exhibited definite luteolytic potential in this species. Equivocal results were obtained with (15S)-15-methyl-PGF2Alpha THAM and its toxic qualities resulted in the demise of three animals.