Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG1000]-b-[PLLA] Multi-Block Copolymers in Healthy Horse Joints

There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG1000]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralateral joints as controls. Blood and synovial fluid were analysed for the tacrolimus concentration and biomarkers for inflammation and cartilage metabolism. After an initial burst release, sustained intra-articular tacrolimus concentrations (>20 ng/mL) were observed during the 42 days follow-up. Whole-blood tacrolimus levels were below the detectable level (<0.5 ng/mL). A transient inflammatory reaction was observed for all substances, evidenced by increases of the synovial fluid white blood cell count and total protein. Prostaglandin and glycosaminoglycan release were increased in joints injected with unloaded monospheres, which was mitigated by tacrolimus. Both tacrolimus-loaded monospheres and HA transiently increased the concentration of collagen II cleavage products (C2C). A histologic evaluation of the joints at the endpoint showed no pathological changes in any of the conditions. Together, these results indicate the good biocompatibility of intra-articular applied tacrolimus-loaded monospheres combined with prolonged local drug release while minimising the risk of systemic side effects. Further evaluation in a clinical setting is needed to determine if tacrolimus-loaded monospheres can be beneficial in the treatment of inflammatory joint diseases in humans and animals.

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Multiple Local Therapeutics Based on Nano-Hydrogel Composites in Breast Cancer Treatment

Journal of Materials Chemistry B ◽

10.1039/d0tb02737e ◽

2020 ◽

Author(s):

Rui-Zhi Tang ◽

Zhen-Zhen Liu ◽

Saisai Gu ◽

Xi-Qiu Liu

Keyword(s):

Breast Cancer ◽

Side Effects ◽

Cancer Treatment ◽

Locoregional Recurrence ◽

Tumor Resection ◽

Local Therapy ◽

Breast Cancer Treatment ◽

Therapy Strategy ◽

Systemic Side Effects ◽

Hydrogel Composites

The locoregional recurrence of breast cancer after tumor resection represents several clinical challenges, and conventional post-surgical adjuvant therapeutics always bring with significant systemic side effects. Thus, the local therapy strategy...

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HYALURONIC ACID IN ORTHOPEDICS

Wiadomości Lekarskie ◽

10.36740/wlek202009114 ◽

2020 ◽

Vol 73 (9) ◽

pp. 1878-1881

Author(s):

Jakub Kosiński ◽

Jaromir Jarecki ◽

Joanna Przepiórka-Kosińska ◽

Magdalena Ratajczak

Keyword(s):

Hyaluronic Acid ◽

Articular Cartilage ◽

Side Effects ◽

Synovial Fluid ◽

Vitreous Body ◽

Invasive Treatment ◽

Inflammatory Reactions ◽

Systemic Side Effects ◽

Inflammatory Drugs ◽

Aseptic Conditions

Hyaluronic acid (HA) as a compound was discovered in 1934 by Karl Meyer and John Palmer as one of the glycosaminoglycans (GAG) in the vitreous body of the bovine eye. HA occurs naturally in many organs, tissues and body fluids, and especially is presented in large quantities in articular cartilage and synovial fluid. It is a non-protein, non-sulfate glycosaminoglycan which has an important role in the physiological biomechanics of synovial fluid, there is responsible for lubrication and drug-elasticity. In the musculoskeletal system, hyaluronic acid is produced by synoviocytes, fibroblasts and chondrocytes. The concentration of hyaluronic acid decreases not only with age, but also in connection with the progression of certain diseases, for example osteoarthritis (OA). For this reason, it has been used for almost 50 years to try to alleviate and treat symptoms of OA in humans and animals. Numerous studies confirmed the beneficial effect of hyaluronic acid supplementation in OA. Patients which has intraarticular viscosupplementation of HA experience less pain and have a reduced need to take nonsteroidal anti-inflammatory drugs. Intra articular HA administration shows a low risk of local and systemic side effects while maintaining proper administration under aseptic conditions. Nevertheless, local inflammatory reactions occur, but it are most often self-limiting or do not require invasive treatment. The issue of recommending hyaluronic acid in osteoarthritis is still ambiguous and controversial.

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Earlobe Keloid Management- A RCT of Intra-Lesional Excision With Intra- & Post-Operative Steroids Versus Intra-Lesional Excision With Post-Operative Steroids

Bangladesh Journal of Plastic Surgery ◽

10.3329/bdjps.v1i1.6489 ◽

1970 ◽

Vol 1 (1) ◽

pp. 24-28

Author(s):

PC Dash ◽

MMT Islam ◽

MS Khondoker ◽

SH Khundkar

Keyword(s):

Side Effects ◽

Steroid Injection ◽

Controlled Trial ◽

Symptomatic Relief ◽

Previous Treatment ◽

Symptomatic Improvement ◽

Steroid Injections ◽

Post Operative Period ◽

Systemic Side Effects

A prospective, randomized controlled trial was designed to compare the outcome of earlobe keloid management by intra-lesional excision with intraoperative and two dose post-operative steroid injections versus intra-lesional excision with two doses post-operative steroid injections. Total 87 patients having 100 earlobe keloids were enrolled in the study with 50 keloids in each group allocated by lottery, but only 69 completed two years follow up. The age of the patients ranged from 15 to 40 years and all were female. Trauma from piercing ear lobule for earring was the main cause of keloid initiation. Both the groups were homogeneous preoperatively regarding age of patients, pre-operative volume of keloids, pattern of previous treatment received, patient's skin complexion and patient’s family history of keloid.Intra-lesional excision keeping 1mm margin followed by intra-operative steroid injection was given in one group and without steroid injection in other group. Residual keloid volume (length, Breath, and height) was measured intra-operatively and post-operatively during follow up period by blindfolded observers. Any symptomatic relief as well as local and systemic side effects of steroids were also recorded.Main observation of this study after two years was 8.3% recurrence in intra-lesional excision with intra-and two dose post-operative steroid injections and 21.2% recurrence in intra-lesional excision with two dose postoperative steroid injections. This difference was not statistically significant (p = 0.177). But, the former protocol reduced recurrence significantly during 1st one year follow up. Residual keloid volume reduction was faster in former protocol in early post-operative period, but not in later period. Symptomatic improvement was also faster in the former protocol, in early post-operative period, but no difference in later period. Local side effects and systemic side effects of steroid were more or less equal in both protocols.The study demonstrates that additional intra-operative steroid injection has better effect in early post-operative period in managing earlobe keloid, but has no significant effect in long term follow up.DOI: http://dx.doi.org/10.3329/bdjps.v1i1.6489Bangladesh Journal of Plastic Surgery (2010) Vol. 1 (1) pp.24-28

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TACROLIMUS OR CYCLOSPORINE FOR IMMUNOSUPPRESSION AFTER HTx: WHICH TREATMENT REVEALS MORE SYSTEMIC SIDE EFFECTS DURING LONG TERM FOLLOW UP?

Transplantation Journal ◽

10.1097/00007890-199904150-00437 ◽

1999 ◽

Vol 67 (7) ◽

pp. S109

Author(s):

B. M. Meiser ◽

D. Schmidt ◽

M. Pfeiffer ◽

W. v. Scheidt ◽

V. Klauss ◽

...

Keyword(s):

Side Effects ◽

Long Term Follow Up ◽

Systemic Side Effects

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Side Effects Reported by Jordanian Healthcare Workers Who Received COVID-19 Vaccines

Vaccines ◽

10.3390/vaccines9060577 ◽

2021 ◽

Vol 9 (6) ◽

pp. 577

Author(s):

Osama Abu-Hammad ◽

Hamza Alduraidi ◽

Shaden Abu-Hammad ◽

Ahmed Alnazzawi ◽

Hamzah Babkair ◽

...

Keyword(s):

Side Effects ◽

Healthcare Workers ◽

Healthcare Professionals ◽

The Public ◽

Systemic Side Effects ◽

The Common ◽

Larger Sample ◽

Local Side

Background Distribution of COVID-19 vaccines has been surrounded by suspicions and rumors making it necessary to provide the public with accurate reports from trustworthy experts such as healthcare professionals. Methods We distributed a questionnaire in Jordan among physicians, dentists and nurses who received a COVID-19 vaccine to explore the side effects (SE) they encountered after the first or the second dose of one of three vaccines namely: AstraZeneca Vaxzevria (AZ), Pfizer-BioNTeck (PB), and SinoPharm (SP) vaccines. Results A total of 409 professionals participated. Approximately 18% and 31% of participants reported no SE after the first dose and second dose, respectively. The remainder had mostly local side effects related to injection site (74%). Systemic side effects in the form of fatigue (52%), myalgia (44%), headache (42%), and fever (35%) prevailed mainly after the first dose. These were significantly associated with AZ vaccine, and age ≤ 45 years (p = 0.000 and 0.01, respectively). No serious SE were reported. Conclusions We can conclude that SE of COVID-19 vaccines distributed in Jordan are within the common range known so far for these vaccines. Further studies are needed to include larger sample size and longer follow-up period to monitor possible serious and long-term SE of the vaccines.

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Laboratory testing of extravascular body fluids: National recommendations on behalf of the Croatian Society of Medical Biochemistry and Laboratory Medicine. Part II – Synovial fluid

Biochemia Medica ◽

10.11613/bm.2020.030501 ◽

2020 ◽

Vol 30 (3) ◽

pp. 371-384

Author(s):

Anja Jokic ◽

Lara Milevoj Kopcinovic ◽

Jelena Culej ◽

Irena Kocijan ◽

Marija Bozovic

Keyword(s):

Quality Of Life ◽

Synovial Fluid ◽

Laboratory Testing ◽

Fluid Collection ◽

Medical Personnel ◽

Laboratory Medicine ◽

Joint Diseases ◽

Prompt Diagnosis

Joint diseases are conditions with an often progressive and generally painful nature affecting the patient’s quality of life and, in some cases, requiring a prompt diagnosis in order to start the treatment urgently. Synovial fluid (SF) laboratory testing is an important part of a diagnostic evaluation of patients with joint diseases. Laboratory testing of SF can provide valuable information in establishing the diagnosis, be a part of a patient’s follow-up and treatment with the purpose of improving the patient’s health and quality of life. Synovial fluid laboratory testing is rarely performed in Croatian medical biochemistry laboratories. Consequently, procedures for SF laboratory testing are poorly harmonized. This document is the second in the series of recommendations prepared by the members of the Working group for extravascular body fluid samples of the Croatian Society of Medical Biochemistry and Laboratory Medicine. It addresses preanalytical, analytical, and postanalytical issues and the clinical significance of tests used in SF laboratory testing with the aim of improving the value of SF laboratory testing in the diagnosis of joint diseases and assisting in the achievement of national harmonization. It is intended for laboratory professionals and all medical personnel involved in synovial fluid collection and testing.

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Nonsurgical Method of Treatment of Childhood Phimosis with the use of Topical Betamethasone

Health Renaissance ◽

10.3126/hren.v8i3.4211 ◽

1970 ◽

Vol 8 (3) ◽

pp. 176-180

Author(s):

BK Rai

Keyword(s):

Side Effects ◽

Prospective Study ◽

Past History ◽

Topical Steroid ◽

Effective Alternative ◽

Surgical Method ◽

History Of Disease ◽

History Of ◽

Systemic Side Effects

Background: Topical steroid application is an effective alternative to circumcision for the treatment of infant and childhood phimosis. Materials & method: prospective study in 42 boys under 13 years of age, with non retractable foreskin with asymptomatic and past history of disease in grade 4 to 6 weeks treatment. the success was defined as full and free retraction, or easy retraction limited only by congenital adhesions to the glans. Results: Forty-two patients completed the treatment. Successful retraction was achieved in 14 (33.33%) at 4 weeks and 32(76.19%) after 6 weeks of application. No adverse systemic side effects were noted. Two patients had failed treatment and were enrolled for circumcision. Two patients refused further treatment. Six patients were lost in subsequent to follow-up. Conclusion: Betamethasone 0.10% ointment is an effective alternative, non surgical method of the treatment for the childhood phimosis. Keywords: Chilhood phimosis; betamethasone DOI: 10.3126/hren.v8i3.4211Health Renaissance, September-December 2010; Vol 8 (No.3);176-180

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Abstract 4098: Epicardial Amiodarone-Releasing Hydrogel Reduces Inducibility of Atrial Fibrillation in Goats

Circulation ◽

10.1161/circ.118.suppl_18.s_828 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Robert W Bolderman ◽

Rob J Hermans ◽

Leonard M Rademakers ◽

Tim S Jansen ◽

Monique M De Jong ◽

...

Keyword(s):

Atrial Fibrillation ◽

Side Effects ◽

Right Atrial ◽

Plasma Drug ◽

Drug Levels ◽

Drug Concentrations ◽

Systemic Side Effects ◽

Novel Strategy ◽

The Right

Amiodarone (AM) is one of the most effective anti-arrhythmic drugs to prevent postoperative atrial fibrillation (AF). However, due to systemic side effects, prophylactic AM therapy is only appropriate for patients at high risk for postoperative AF. This study addressed the hypothesis that local epicardial delivery of AM produces therapeutic myocardial drug concentrations, while systemic levels remain low. Goats (n=14) were instrumented with right atrial epicardial patch electrodes, and a PEG-based hydrogel with AM (1 mg/kg bw) (n=9) or without drug (n=5) was applied to the right atrial epicardium. AF inducibility was assessed up to 28 days in awake goats by applying burst stimuli. Myocardial and plasma AM concentrations were analysed by HPLC. AM-hydrogel produced higher subepicardial than subendocardial drug concentrations, which both remained therapeutic up to 21 days after hydrogel application (fig. 1a ). In this period, AF inducibility was significantly lower in the AM-hydrogel group compared to hydrogel alone (fig. 1b ; p<0.05). Plasma AM and metabolite levels were below detection limits (<30 ng/L) during the 28-day follow-up. Epicardial AM-releasing hydrogel produces sufficient myocardial drug concentrations to reduce AF inducibility up to 3 weeks, whereas plasma drug levels remain undetectably low. This study demonstrates that local delivery of anti-arrhythmic drugs is a feasible approach to obtain therapeutically effective myocardial drug concentrations, while minimizing risk for systemic side effects. Locally applied AM-releasing hydrogel may be a novel strategy to prevent postoperative AF. Figure 1a. Amiodarone Distribution in Right Atrium (n=5) Figure 1b. AF Inducibility After Hydrogel Application (mean + SD)

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Intralesional Bleomycin for the Treatment of Resistant Palmoplantar and Periungual Warts

Dermatology Research and Practice ◽

10.1155/2021/8655004 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Suchana Marahatta ◽

Dhan Keshar Khadka ◽

Sudha Agrawal ◽

Arpana Rijal

Keyword(s):

Retrospective Study ◽

Side Effects ◽

Treatment Response ◽

Efficacy And Safety ◽

Poor Treatment ◽

Systemic Side Effects ◽

The Mean ◽

Plantar Warts ◽

Poor Treatment Response

Introduction. Periungual, palmar, and plantar warts are difficult to treat with poor treatment response. Intralesional (IL) bleomycin has shown promising results for their treatment in a few reports. However, we need further evidence before opting it for treating difficult sites and resistant warts. Hence, we conducted this study to assess the efficacy and safety of IL bleomycin for the treatment of resistant palmoplantar and periungual warts. Methods. In this retrospective study, we included all patients who were given IL bleomycin for warts over a year. Maximum three sittings of bleomycin (1 mg/ml) were given monthly, and they were followed up for 3 months after the procedure. The response was categorized as complete, near-complete, significant, moderate, mild, and no clearance for 100%, 75–99%, 50–74%, 25–49%, 1–25%, and 0% clearance, respectively. Results. Out of 29 patients, follow-up details were available only in 19 patients (53 warts). The mean duration was 2.5 ± 1.47 years. The number of past interventions ranged from 2–4. Wart clearance after the first intervention was complete in 36.84%, near-complete in 26.31%, significant in 26.31%, and moderate in 10.53%. Wart clearance after the last intervention was complete in 89.47% and near-complete in 10.52% of patients. However, during 3 months of follow-up after the last injection, 15.78% had a recurrence. None of them had severe local and systemic side effects. Conclusions. IL bleomycin could be a better treatment option for the treatment of resistant and difficult warts. However, we observed a higher recurrence rate even in a shorter follow-up. Hence, we need further studies with larger samples.

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Endovenous radiofrequency powered segmental thermal ablation (Closure FAST) of great saphenous veins

Phlebologie ◽

10.1055/s-0037-1622301 ◽

2010 ◽

Vol 39 (02) ◽

pp. 69-71 ◽

Cited By ~ 6

Author(s):

T. M. Proebstle ◽

Keyword(s):

Side Effects ◽

Thermal Ablation ◽

Clinical Success ◽

Clinical Success Rate ◽

Duplex Ultrasound ◽

Multicenter Trial ◽

Saphenous Veins ◽

Clinical Control ◽

Prospective Multicenter Trial

Summary Background: Radiofrequency powered segmental thermal ablation Closure FAST has become a globally engaged technology for ablation of incompetent great saphenous veins (GSVs). Mid-term results of slowly resolving side effects are still not described. Methods: RSTA-treated GSVs (n = 295) were followed for 24 months in a prospective multicenter trial. Clinical control visits included flow and reflux analysis by duplex-ultrasound and assessment of treatment related side effects at all times. Results: 280 of 295 treated GSVs (94.9%) were available for 24 months follow-up. According to the method of Kaplan and Meier at 24 months after the intervention 98.6% of treated legs remained free of clinically relevant axial reflux. The average VCSS score improved from 3.9 ± 2.1 at screening to 0.7 ± 1.2 at 24 months follow-up (p < 0.0001). While only 41.1% of patients were free of pain before treatment, at 24 months 99.3% reported no pain and 96.4% did not experience pain during the 12 months before. At 24 months n=3 legs showed pigmentation along the inner thigh and one leg showed study-treatment related paresthesia. Conclusion: Radiofrequency powered segmental thermal ablation Closure FAST showed a very moderate side-effect profile in conjunction with a high and durable clinical success rate.

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