Smart contact lens systems for ocular drug delivery and therapy.

Ocular drug delivery and therapy systems have been extensively investigated with various methods including direct injections, eye drops and contact lenses. Nowadays, smart contact lens systems are attracting a lot of attention for ocular drug delivery and therapy due to their minimally invasive or non-invasive characteristics, highly enhanced drug permeation, high bioavailability, and on-demand drug delivery. Furthermore, smart contact lens systems can be used for direct light delivery into the eyes for biophotonic therapy replacing the use of drugs. Here, we review smart contact lens systems which can be classified into two groups of drug-eluting contact lens and ocular device contact lens. More specifically, this review covers smart contact lens systems with nanocomposite-laden systems, polymeric film-incorporated systems, micro and nanostructure systems, iontophoretic systems, electrochemical systems, and phototherapy systems for ocular drug delivery and therapy. After that, we discuss the future opportunities, challenges and perspectives of smart contact lens systems for ocular drug delivery and therapy.

The effect of lidocaine iontophoresis for the treatment of tinnitus: a systematic review.

PURPOSE: Tinnitus is a common symptom with multiple causes and treatment options. Previous studies have investigated the effect of lidocaine iontophoresis. The aim of this review is to systematically present the effects on tinnitus and to derive possible effects. METHODS: In accordance to the PRISMA statement, the search and analysis were performed. An abstract in German or English and a performed intervention with lidocaine iontophoresis for the treatment of tinnitus, independent of the study design, were considered as inclusion criteria. Due to the heterogeneity of the studies, only a narrative synthesis was performed. RESULTS: The search yielded 179 studies of which 170 were excluded. Six full-texts and three abstracts were included. In total, 957 patients were treated with lidocaine iontophoresis. The percent improvement in symptoms after lidocaine iontophoresis ranged from 4% to 62%. The qualitative assessment of the studies resulted in an overall "weak" rating for all of them. CONCLUSIONS: Due to the heterogeneity and the limited quality of the studies found, no clear statement can be made about the efficacy. The number of those who benefited from therapy varied widely. In addition, it cannot be ruled out that the effect was merely due to electrical stimulation of the cochlea.

Iontophoresis Corneal Cross-linking With Oxygen Supplementation in Ovine Eyes.

PURPOSE: To evaluate the biomechanical changes and advanced oxidation protein products (AOPP) production after different corneal cross-linking (CXL) protocols with or without oxygen supplementation. METHODS: Ovine eyes in the study were equally distributed to five groups as control, standard Dresden protocol, diluted alcohol- and iontophoresis-assisted CXL (DAI-CXL), and 0.1% and 0.2% riboflavin-mediated iontophoresis-assisted CXL with oxygen supplementation (I-CXL). Corneas that received CXL were divided into two equal parts, one part was used for uniaxial tensiometry and one part was used for AOPP measurement. RESULTS: All treatment groups showed higher Young's modulus and stiffness compared to the control group (P < .05). Both oxygen-assisted I-CXL groups with 0.1% and 0.2% riboflavin concentrations had higher corneal Young's modulus (P = .009 and .006, respectively) and stiffness (P = .009) values, whereas the DAI-CXL group had lesser Young's modulus and stiffness values (P = .032) compared to the Dresden protocol group. All treatment groups showed higher AOPP concentrations compared to the control group (P < .05). DAI-CXL and I-CXL groups showed similar AOPP formation compared to the Dresden protocol (P = .673). CONCLUSIONS: When the epithelium is intact, the desired increase in corneal stiffness might not be achieved. However, increasing the oxygen in the environment might provide a sufficient increase in stiffness in cases undergoing epitheliumon I-CXL, which might be promising in terms of shortening the CXL therapy and decreasing the complications. [J Refract Surg. 2022;38(10):674-681.].

Iontophoresis of treprostinil promotes wound healing in a murine model of scleroderma-related ulcers.

OBJECTIVE: Systemic sclerosis (SSc) is a rare, chronic disease characterized by fibrosis, vascular alterations and digital ulcerations. Few drugs have shown efficacy to enhance wound healing of existing SSc-related ulcers. Local delivery of treprostinil, a prostacyclin analogue, may improve wound healing. The present work aimed first at developing a mouse model of SSc-related ulcerations and second at assessing the effect of iontophoresis of treprostinil on wound healing. METHODS: We used two murine models of SSc: chemically induced with HOCl, and urokinase-type plasminogen activator receptor (uPAR)-deficient. Excisional wounding was performed on the dorsal midline with a biopsy punch. Animals were randomized into three groups: treated with electrostimulation alone, with treprostinil iontophoresis or untreated. We assessed wound healing over time, as well as skin microvascular reactivity, inflammation, microvessel density and collagen distribution, before wounding and after re-epithelialization. RESULTS: uPAR-/- mice, but not HOCl-treated mice, showed impaired wound healing and decreased microvascular reactivity compared with their controls. Treprostinil iontophoresis improved wound healing and microvascular density and decreased inflammation in uPAR-/- mice, while electro-stimulation did not. However, treprostinil had no effect on microvascular reactivity and collagen distribution. CONCLUSION: This study suggests that excisional wounds in uPAR-/- mice are a relevant model of SSc-related ulcers. In addition, treprostinil iontophoresis enhances wound healing in this model. Further work in now needed to show whether this effect translates in humans.

The effect of galvanization and potassium iodide iontophoresis of the throat and larynx on thyroid parameters: a randomized controlled trial.

Few studies have assessed the application and side effects of potassium iodide (KI) iontophoresis. Using a double-blinded randomized controlled trial with a 1:1 parallel-group, we investigated the effect of galvanization and the KI iontophoresis in the throat and larynx on three thyroid parameters. A total of 50 healthy volunteers with normal TSH, FT3, and FT4 levels and lacking focal changes in the thyroid ultrasonography were subjected to 10 electrotherapy treatments. The TSH, FT3, and FT4 levels were determined prior to the 10 electrotherapeutic treatments (T1), 2-weeks after treatment (T2) and 6-months after treatment (T3). At T2 and T3, both groups had normal levels of TSH, FT3, and FT4. Regarding the change of TSH, FT3, and FT4 levels between T1 vs. T2 and T1 vs. T3, no significant differences between the galvanization and iontophoresis groups were found. However, both groups had lower levels of all three hormones at T3. Together, these data indicate that KI iontophoresis does not affect thyroid hormone levels in the short- nor long-term. Additional follow-up studies with larger groups are required to better confirm the safety of galvanization and iontophoresis procedures in the pharynx and larynx.Trial registration ClinicalTrials.gov (NCT04013308; URL: www.clinicaltrials.gov ). Day of first registration 09/07/2019.

Delivery systems for improving iron uptake in anemia.

Anemia poses a threat to a broad population globally as depleted hemoglobin leads to a plethora of conditions, and the most common cause includes iron deficiency. Iron is an essential element important for erythropoiesis, DNA synthesis, protection of the immune system, energy production, and cognitive function and hence should be maintained at appropriate levels. Various proteins are involved in transporting and absorption of iron, activation of heme synthesis, and RBC production that could be possible targets to improve iron delivery. Oral supplementation of iron either from dietary or synthetic sources has been the frontline therapy for treating iron deficiency in anemia. At the same time, intravenous administration is provided in chronic anemia, such as chronic kidney diseases (CKD). This review focuses on the strategies developed to overcome the disadvantages of available iron therapies and increase iron absorption and uptake in the body to restore iron content. Nanotechnology combined with the food fortification processes gained attention as they help develop new delivery systems to improve iron uptake by enterocytes. Furthermore, naturally obtained products such as polysaccharides, peptides, proteins, and new synthetic molecules have been used in fabrication of iron-carrier systems. The establishment of transdermal iron delivery systems such as microneedle arrays or iontophoresis, or the discovery of new molecules also proved to be an effective way for delivering iron in patients non-compliant to oral therapy.

In Vitro and in Vivo Comparative Study of Oral Nanoparticles and Gut Iontophoresis as Oral Delivery Systems for Insulin.

Multiple daily injections of insulin for diabetes cause many hazards for diabetic patients. Oral noninvasive insulin delivery could be more convenient and less painful than parenteral route. In past decades transdermal iontophoresis had been studied for insulin delivery across the skin with or without chemical permeation enhancers. However, the results of these studies were not efficacious and serum insulin levels were not therapeutically effective. In the present study an advanced technology "gut iontophoresis" for insulin delivery across the gut wall was compared with traditional oral insulin delivery in the form of nanoparticles. In vitro application of electric current to the intestinal membrane could enhance the flux of insulin nanoparticles (3.4 fold enhancement of insulin transport) from the donor to the receptor compartment in the Franz cell. In vivo iontophoresis of insulin nanoparticles through the gut wall would produce intense hypoglycemia (57% glycemia drop in 3 h) without damage of the intestinal tissues. Cell viability assay indicated that 50-500 µg/mL nanoparticles had no toxic effect on Caco-2 cells. Nanoparticles gut iontophoresis could be a promising non-invasive technique for oral insulin delivery.

Iontophoresis to Overcome the Challenge of Nail Permeation: Considerations and Optimizations for Successful Ungual Drug Delivery.

Iontophoresis is a widely used drug delivery technique that has been used clinically to improve permeation through the skin for drugs and other actives in topical formulations. It is however not commonly used for the treatment of nail diseases despite its potential to improve transungual nail delivery. Instead, treatments for nail diseases are limited to relatively ineffective topical passive permeation techniques, which often result in relapses of nail diseases due to the thickness and hardness of the nail barrier resulting in lower permeation of the actives. Oral systemic antifungal agents that are also used are often associated with various undesirable side effects resulting in low patient compliance. This review article discusses what is currently known about the field of transungual iontophoresis, providing evidence of its efficacy and practicality in delivering drug to the entire surface of the nail for extended treatment periods. It also includes relevant details about the nail structure, the mechanisms of iontophoresis, and the associated in vitro and in vivo studies which have been used to investigate the optimal characteristics for a transungual iontophoretic drug delivery system. Iontophoresis is undoubtedly a promising option to treat nail diseases, and the use of this technique for clinical use will likely improve patient outcomes.Graphical abstract.

Iontophoresis mediated localized delivery of liposomal gold nanoparticles for photothermal and photodynamic therapy of acne.

Acne is one of the common dermatological skin inflammatory conditions. The current therapeutic modalities for the treatment of acne include the administration of antibiotics and anti-inflammatory agents. The rising instance of antibiotic resistance in acne strains has led to the exploration of alternative therapeutic modalities. In the current study, we have employed a liposomal gold nanoparticle entrapping curcumin (Au Lipos Cur NPs) for dual light-mediated therapy for the treatment of acne. These nanoparticles exerted a positive zeta potential that enabled their localized follicular delivery by iontophoresis. The localized deposition of Au Lipos NPs leads to photothermal transduction causing destruction of sebaceous glands. Furthermore, when the nanoparticles were assessed in vitro by sequential irradiation with NIR and blue light, it resulted in significant inhibition of bacterial growth. Thus the dual light-mediated therapy by Au Lipos Cur NPs can form a potential therapeutic modality for the efficient treatment of recurrent acne.

Management of chronic hand and foot eczema. An Australia/New Zealand Clinical narrative.

Chronic hand/foot eczemas are common, but treatment is often challenging, with widespread dissatisfaction over current available options. Detailed history is important, particularly with regard to potential exposure to irritants and allergens. Patch testing should be regarded as a standard investigation. Individual treatment outcomes and targets, including systemic therapy, should be discussed early with patients, restoring function being the primary goal, with clearing the skin a secondary outcome. Each new treatment, where appropriate, should be considered additive or overlapping to any previous therapy. Management extends beyond mere pharmacological or physical treatment, and requires an encompassing approach including removal or avoidance of causative factors, behavioural changes and social support. To date, there is little evidence to guide sequences or combinations of therapies. Moderately symptomatic patients (e.g. DLQI ≥ 10) should be started on a potent/super-potent topical corticosteroid applied once or twice per day for 4 weeks, with tapering to twice weekly application. If response is inadequate, consider phototherapy, and then a 12-week trial of a retinoid (alitretinoin or acitretin). Second line systemic treatments include methotrexate, ciclosporin and azathioprine. For patients presenting with severe symptomatic disease (DLQI ≥ 15), consider predniso(lo)ne 0.5-1.0 mg/kg/day (or ciclosporin 3 - 5 mg/kg/day) for 4-6 weeks with tapering, and then treating as for moderate disease as above. In non-responders, botulinum toxin and/or iontophoresis, if associated with hyperhidrosis, may sometimes help. Some patients only respond to long-term systemic corticosteroids. The data on sequencing of newer agents, such as dupilumab or JAK inhibitors, are immature.

Acupuncture Combined with Chinese Medicine Iontophoresis Treatment for Chronic Progressive Cervical Intervertebral Disk Disease in a Dog.

CASE REPORT: A 12-year-old castrated male dog with nonambulatory tetraplegia was diagnosed with spinal stenosis at C3-C4 through X-ray examination and with ventral extradural spinal compression at C3-C4 through myelography and computed tomography. The diagnosis of traditional Chinese veterinary medicine was local Qi and blood stagnation, spleen Qideficiency, blood deficiency, and kidney Yang deficiency. We initiated treatment using a combination of acupuncture and Chinese medicine iontophoresis with laser therapy. After 12 treatment days, there was a significant improvement in the dog's ambulation function, which was indicated by proper walking and flexible head-turning. CONCLUSION: This indicates that combining acupuncture and Chinese medicine iontophoresis could be a potential treatment for chronic progressive cervical intervertebral disk disease in dogs.

Intra tester reliability of sympathetic skin responses in subjects with primary palmar hyperhidrosis.

BACKGROUND: Primary palmar hyperhidrosis (PPH) is a disorder related to sympathetic dysfunction. Iontophoresis can be used to reduce sweating rate. Sympathetic skin response (SSR) is commonly used to evaluate the sympathetic system. However, scarce evidence exists about the reliability of SSR parameters. OBJECTIVE: To assess the relative and absolute reliability of SSR before and after the application of iontophoresis with aluminum chloride hexahydrate (ACH) gel or tap water in subjects with PPH. METHODS: Twenty subjects were randomized to receive either iontophoresis with ACH gel or tap water. Three SSRs (amplitude and latency) with 5 s intervals from both hands in both groups were recorded before and after the application of iontophoresis for 30 min. Reliability of amplitude and latency of the SSR was assessed using intraclass correlation coefficient (ICC) with 95% confidence intervals, standard error of measurement (SEM), and minimal detectable change (MDC). RESULTS: Amplitudes and latencies of SSR showed good to excellent test-retest reliability for ICC in both groups before iontophoresis. Except for right hand latency which was moderate (0.5-0.75). After iontophoresis, the ACH gel group still showed good to excellent agreement for SSR parameters, while the reliability of SSR parameters in the tap water group was reduced. CONCLUSION: Subjects with PPH showed high intra-rater reliability for SSR parameters which was maintained after ACH gel iontophoresis and decreased after tap water iontophoresis. It seems that media used for iontophoresis or the state of media (gel vs liquid) may affect the reliability of SSR. Further research is recommended.

Effects of Ice Massage Prior to an Iontophoresis Treatment Using Dexamethasone Sodium Phosphate.

CONTEXT: Low current intensity iontophoresis treatments have increased skin perfusion over 700% from baseline potentially altering drug clearance from or diffusion to the targeted area. OBJECTIVE: To determine the effects of a preceding 10-minute ice massage on subcutaneous dexamethasone sodium phosphate (Dex-P) concentration and skin perfusion during and after a 4-mA iontophoresis treatment. DESIGN: Controlled laboratory study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-four participants (male = 12, female = 12; age = 25.6 [4.5] y, height = 173.9 [8.51] cm, mass = 76.11 [16.84] kg). INTERVENTION(S): Participants were randomly assigned into 2 groups: (1) pretreatment 10-minute ice massage and (2) no pretreatment ice massage. Treatment consisted of an 80-mA·minute (4 mA, 20 min) Dex-P iontophoresis treatment. Microdialysis probes (3 mm deep in the forearm) were used to assess Dex-P, dexamethasone (Dex), and its metabolite (Dex-Met) concentrations. Skin perfusion was measured using laser Doppler flowmetry. MAIN OUTCOME MEASURE(S): Microdialysis samples were collected at baseline, at conclusion of treatment, and every 20 minutes posttreatment for 60 minutes. Samples were analyzed to determine Dex-Total (Dex-Total = Dex-P + Dex + Dex-Met). Skin perfusion was calculated as a percentage change from baseline. A mixed-design analysis of variance was used to determine Dex-Total and skin perfusion difference between groups overtime. RESULTS: There was no difference between groups (P = .476), but [Dex-Total] significantly increased over the course of the iontophoresis and posttreatment time (P < .001). Dex-P was measured in 18 of 24 participants with a mean concentration of 0.67 (1.09) µg/mL. Skin perfusion was significantly greater in the no ice treatment group (P = .002). Peak skin perfusion reached 27.74% (47.49%) and 117.39% (103.45%) from baseline for the ice and no ice groups, respectively. CONCLUSIONS: Ice massage prior to iontophoresis does not alter the tissue [Dex-Total] even with less skin perfusion.

Physical therapy for tendinopathy: An umbrella review of systematic reviews and meta-analyses.

OBJECTIVE: To summarize evidence in the last decade regarding the efficacy of physical therapy interventions to treat tendinopathy, as a single disease entity, as determined in systematic reviews (SRs) and/or meta-analyses (MAs). METHODS: Electronic search of PubMed, PEDro, and Scopus database was performed from year 2010 to January 2020. The methodological quality of the identified studies was assessed using the AMSTAR 2 tool. Studies scoring 9 points or higher were further analyzed using GRADE principles. RESULTS: 40 SRs and/or MAs were included in qualitative synthesis, whereas only 5 MAs were included in quantitative synthesis. Low-level laser therapy (LLLT) intervention showed a pooled improvement in pain reduction of 1.53 cm; 95% CI, [1.14, 1.91] (I2 = 1.9%, p = 0.361) on visual analogue scale, and grip strength of 9.59 kg; 95% CI, [5.90, 13.27]. CONCLUSIONS: Moderate-quality evidence may support these following interventions: LLLT revealed a statistically and potentially clinically significant improvement in pain and function on the short-term. Extracorporeal shockwave therapy showed a statistically significant enhancement in pain and function at all follow-up durations; however, its clinical significance was undetermined. Eccentric exercise was supported by qualitative evidence only. Caution is advised when interpreting results due to possible pathological differences in tendinopathy at each region.

Iontophoresis-Assisted Rose Bengal and Green Light Corneal Cross-Linking.

PURPOSE: To evaluate the effects of the application of iontophoresis-assisted rose bengal and green light cross-linking (I-RGX) therapy on enucleated rabbit eyes for corneal biomechanical parameters, dye diffusion rates, and green light levels reaching deep tissues and to compare these parameters with a standard rose bengal and green light cross-linking (RGX) therapy. METHOD: Forty-five enucleated rabbit eyes were used in this study. To evaluate biomechanical changes, corneas were divided into the following 4 groups: the control group, the 0.1% rose bengal application group, the RGX group (100 J/cm), and the I-RGX group (100 J/cm). After this, corneal strips were evaluated with a uniaxial extensometer. To assess corneal dye diffusion, postprocedure dye depth was recorded with anterior segment optic coherence tomography. The amount of irradiation passing through the cornea during irradiation with 250 mW/cm irradiation power was measured with a laser power meter at the first, third, and seventh minutes. RESULTS: In the I-RGX-treated group especially, the mean elastic modulus and corneal stiffness values were about 4.7 times higher when compared with the controls and about 2.2 times higher than those in the RGX group. The rose bengal diffusion depth was 26.63% ± 3.84% of the total corneal thickness in the rose bengal drop group, but this value increased to 42.22% ± 4.77% in the iontophoresis group (<0.001). After iontophoresis, an average of 98% of the 100 J/cm green light was kept in the cornea. CONCLUSIONS: I-RGX is a very useful method for increasing corneal biomechanical strength and is highly effective in increasing the amount of corneal dye diffusion into the cornea while also minimalizing the amount of laser passage reaching deeper tissues.

Physical triggering strategies for drug delivery.

Physically triggered systems hold promise for improving drug delivery by enhancing the controllability of drug accumulation and release, lowering non-specific toxicity, and facilitating clinical translation. Several external physical stimuli including ultrasound, light, electric fields and magnetic fields have been used to control drug delivery and they share some common features such as spatial targeting, spatiotemporal control, and minimal invasiveness. At the same time, they possess several distinctive features in terms of interactions with biological entities and/or the extent of stimulus response. Here, we review the key advances of such systems with a focus on discussing their physical mechanisms, the design rationales, and translational challenges.

In-Office Tympanostomy Tube Placement in Children Using Iontophoresis and Automated Tube Delivery.

OBJECTIVES/HYPOTHESIS: Evaluate technical success, tolerability, and safety of lidocaine iontophoresis and tympanostomy tube placement for children in an office setting. STUDY DESIGN: Prospective individual cohort study. METHODS: This prospective multicenter study evaluated in-office tube placement in children ages 6 months through 12 years of age. Anesthesia was achieved via lidocaine/epinephrine iontophoresis. Tube placement was conducted using an integrated and automated myringotomy and tube delivery system. Anxiolytics, sedation, and papoose board were not used. Technical success and safety were evaluated. Patients 5 to 12 years old self-reported tube placement pain using the Faces Pain Scale-Revised (FPS-R) instrument, which ranges from 0 (no pain) to 10 (very much pain). RESULTS: Children were enrolled into three cohorts with 68, 47, and 222 children in the Operating Room (OR) Lead-In, Office Lead-In, and Pivotal cohorts, respectively. In the Pivotal cohort, there were 120 and 102 children in the <5 and 5- to 12-year-old age groups, respectively, with a mean age of 2.3 and 7.6 years, respectively. Bilateral tube placement was indicated for 94.2% of children <5 and 88.2% of children 5 to 12 years old. Tubes were successfully placed in all indicated ears in 85.8% (103/120) of children <5 and 89.2% (91/102) of children 5 to 12 years old. Mean FPS-R score was 3.30 (standard deviation [SD] = 3.39) for tube placement and 1.69 (SD = 2.43) at 5 minutes postprocedure. There were no serious adverse events. Nonserious adverse events occurred at rates similar to standard tympanostomy procedures. CONCLUSIONS: In-office tube placement in selected patients can be successfully achieved without requiring sedatives, anxiolytics, or papoose restraints via lidocaine iontophoresis local anesthesia and an automated myringotomy and tube delivery system. LEVEL OF EVIDENCE: 2b Laryngoscope, 130:S1-S9, 2020.

How strong is the evidence that conservative treatment reduces pain and improves function in individuals with patellar tendinopathy? A systematic review of randomised controlled trials including GRADE recommendations.

OBJECTIVE: To determine the effectiveness of conservative treatment (CT) on pain and function in patients with patellar tendinopathy (PT) compared with minimal intervention (MI) or other invasive intervention, or in addition to decline eccentric squat. METHODS: Searches were performed in MEDLINE, Embase, Cochrane, PEDro, SPORTDiscus, CINAHL and AMED databases. All randomised trials that evaluated CT (any intervention not involving invasive procedures or medication) in individuals with PT were included. Two reviewers screened studies, extracted data and assessed risk of bias of all included studies. Where suitable, meta-analyses were conducted; we assessed certainty of the evidence using GRADE methodology. RESULTS: When compared with MI, CT did not improve pain (weighted mean difference (WMD) -2.6, 95% CI -6.5 to 1.2) or function (WMD 1.8, 95% CI -2.4 to 6.1) in the short-term (up to 3 months) follow-up. When compared with invasive intervention, CT did not improve pain (WMD 0.7, 95% CI -0.1 to 1.4) or function (WMD -6.6, 95% CI -13.3 to 0.2) in the short-term follow-up. No overall effects were found for combined CT (when a conservative intervention was added to decline eccentric squat) on pain (WMD -0.5, 95% CI -1.4 to 0.4) or function (WMD -2.3, 95 % -9.1 to 4.6) at short-term follow-up. Single studies showed an effect on pain with iontophoresis at short-term follow-up (d = 2.42) or dry needling at medium/long-term follow-up (d = 1.17) and function with exercise intervention at medium/long-term follow-up (over 3 months) (d = 0.83). SUMMARY/CONCLUSION: Our estimates of treatment effect have only low to very low certainty evidence to support them. This field of sports medicine/sports physiotherapy urgently needs larger, high-quality studies with pain and function among the potential primary outcomes.

The short-term effectiveness of low-level laser, phonophoresis, and iontophoresis in patients with lateral epicondylosis.

STUDY DESIGN: Randomized parallel group trial. INTRODUCTION: Various treatment options for lateral epicondylosis have been reported in the literature. PURPOSE OF STUDY: We aimed to compare the effectiveness of low-level laser therapy (LLLT), phonophoresis, and iontophoresis in terms of pain, function, and grip strength. METHODS: This study that comprised 37 patients with lateral epicondylosis was planned as a prospective randomized parallel group trial. Twelve participants were randomized to the LLLT group, 12 to the phonophoresis group, and 13 to the iontophoresis group. The Visual Analog Scale (VAS), pressure algometer, the Patient-Rated Tennis Elbow Evaluation, and grip strength dynamometer were used to measure outcomes. The measurements were performed at baseline and at the end of 15 sessions. RESULTS: Investigation of the pain scores revealed that all VAS scores were improved in both the laser and iontophoresis groups (VAS at rest: P = .015, effect size (ES) = 1.49 and P = .016, ES = 0.58, respectively; VAS during activity: P = .008, ES = 1.05 and P = .008, ES = 1.16, respectively; VAS at night: P = .013, ES = 1.01 and P = .016, ES = 0.72, respectively). Only advance in function and grip strength was associated with the iontophoresis group (Patient-Rated Tennis Elbow Evaluation P = .006, ES = 0.78; grip strength with elbow extension P = .011, ES = 1.03; with elbow flexion P = .003, ES = 0.52). DISCUSSION: The most effective approach could not be highlighted among the existing studies in the literature as they were applied in combination with other therapies. CONCLUSION: In our study, we observed that LLLT provides a benefit only for pain, whereas iontophoresis is beneficial for both pain and function. If the effect size is evaluated, LLLT is more influential than iontophoresis for decreasing pain. However, when we compared phonophoresis and iontophoresis in terms of effectiveness, we found that iontophoresis has better effects for pain, function, and grip strength.

Effects of dietary supplementation with creatine on homocysteinemia and systemic microvascular endothelial function in individuals adhering to vegan diets.

The incidence of cardiovascular diseases in vegetarian individuals is lower than that in the general population. Nevertheless, individuals who adhere to vegan diets have a higher prevalence of hyperhomocysteinemia with eventual adverse effects on vascular reactivity. Creatine supplementation (CrS) reduces plasma homocysteine levels and enhances vascular reactivity in the microcirculation. Thus, we investigated the effects of CrS on systemic microcirculation and homocysteine blood levels in strict vegan subjects. Forty-nine strict vegan subjects were allocated to the oral CrS (5 g micronized creatine monohydrate daily for three weeks; n = 31) and placebo (n = 18) groups. Laser speckle contrast imaging coupled with acetylcholine skin iontophoresis was used to evaluate cutaneous microvascular reactivity, and intravital video-microscopy was used to evaluate skin capillary density and reactivity before and after CrS. We demonstrated that CrS reduces the plasma levels of homocysteine and increases those of folic acid. After the CrS period, the homocysteine levels of all of the vegan subjects normalized. CrS also induced increases in baseline skin functional capillary density and endothelium-dependent capillary recruitment in both normo- (N-Hcy) and hyperhomocysteinemic (H-Hcy) individuals. CrS increased endothelium-dependent skin microvascular vasodilation in the H-Hcy vegan subjects but not in the N-Hcy vegan subjects. In conclusion, three weeks of oral CrS was sufficient to increase skin capillary density and recruitment and endothelium-dependent microvascular reactivity. CrS also resulted in plasma increases in folic acid levels and reductions in homocysteine levels among only the H-Hcy individuals.