31-gauge Needle Research Articles

Pain perception in 4-6-year-old children following intraoral dental injection with 26 and 31-gauge needles: a randomized controlled trial.

Administering anesthesia in dentistry can be distressing for patients, especially those with dental fear and anxiety. Needle pain during local anesthesia is a common concern in intraoral procedures. This study aimed to compare pain perception in 4-6-year-old children following intraoral dental injections with 26- and 31-gauge needles. Fifty healthy children were divided according to age into Group I (N = 25; 4-5 years) and Group II (N = 25; 5-6 years). Each group was further subdivided according to the needle gauge as follows: Group IA (26 gauge), Group IB (31 gauge), Group IIA (26 gauge), and Group IIB (31 gauge). Using a lottery method, the gauge of the needle to be used at the first visit for local anesthesia administration was selected. Children's reactions to pain were evaluated using a Modified Behavioral Pain Scale. Immediately after administration of local anesthesia, pain perception was evaluated using the Faces pain rating scale. In the subsequent visit, another needle gauge was used to administer local anesthesia, and the previously described evaluations were performed. At the third appointment, the child was shown both syringes and asked to choose one of the syringes they preferred, and the choice was noted. When local anesthesia was administered using a 31-gauge needle, pain perception was similar between the two groups. In group II, the children demonstrated significantly higher arm and leg movements (P = 0.001). However, the difference was significant in group I alone (P < 0.001). Irrespective of age, anesthesia with a 31-gauge needle resulted in significantly lower pain perception than anesthesia with a 26-gauge needle.

Clinical Features Associated with Acute Elevated Intraocular Pressure After Intravitreal Anti-VEGF Injections.

To study the effects of intravitreal injection (IVI) of anti-VEGF (vascular endothelial growth factor) agents on intraocular pressure (IOP) and find associations with acute pressure spikes. This was a three-month, prospective study of patients receiving outpatient IVI of anti-VEGF agents for diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) at the Acuity Eye Group Medical Centers. IOP was measured pre- and post-injection at 10-minute intervals up to 50 minutes after injection with a handheld tonometer. Patients with an IOP greater than 35 mmHg at 30 minutes received an anterior chamber paracentesis (ACP), while patients below 35 mmHg were monitored without intervention. A total of 617 patients (51% female, 49% male) received IVI for DR (n = 199), AMD (n = 355), and RVO (n = 63). ACP was performed in 17 patients. Average pre-injection IOP was 16 ± 4 compared to 24 ± 7 mmHg for the non-ACP vs ACP group, respectively (mean ± standard deviation), p < 0.0001. IOP returned to baseline in 98% of patients at 50 minutes. A diagnosis of glaucoma and glaucoma suspect was more prevalent in the ACP group compared to the non-ACP group, 82.3% vs 14.2% and 17.6% vs 9.0%, respectively, p < 0.0001 and p > 0.05. Patients with a pre-injection IOP >25 mmHg and a history of glaucoma had a 58.3% rate of ACP. A 31-gauge needle had a higher mean increase in IOP from baseline compared to 30-gauge needle, p < 0.0001. IOP spikes are most significant in the first 10 minutes after IVI but typically resolve within the first hour. However, utilizing a smaller 31-gauge IVI in patients with a glaucoma history and pre-injection IOP >25 mmHg may be associated with significant IOP spikes lasting longer than 30 minutes.

Evaluation of the Antibacterial Efficacy of QMix and AgNP Solutions in Root Canals of Primary Molars: An In-Vitro Study.

PurposeThe study aimed to evaluate QMix2in1 and silver nanoparticles (AgNPs) solution in eliminating Enterococcus faecalis (E. faecalis) bacteria within root canals of primary molars.Materials and methodsThe study sample consisted of 45 extracted primary molars, which were divided into three groups: Group 1 (control) NaOCl 5.25%, Group 2 (experimental) QMix2 in 1, and Group 3 (experimental) AgNPs 4000 ppm. The root canals were sterilized within an autoclave and then contaminated with E. faecalis bacteria. The root canals were irrigated for five minutes in a quantity of 3 ml using a 31-gauge irrigation needle, and then bacterial smears were taken.ResultsSodium hypochlorite, AgNPs, and QMix2in1 effectively reduced the bacterial count of Enterococcus within root canals of primary molars. There were statistical differences between all groups. QMix2in1 solution showed the greatest antibacterial efficacy, then NaOCl solution and AgNPs solution. ConclusionAll irrigation solutions used are effective in eliminating E. faecalis. QMix2in1 can be considered a good alternative to sodium hypochlorite in irrigation root canals of primary teeth.

Perineural 5% Dextrose Injection Treatment and Central Core Excision of the 12:00 Vestibule as Adjunctive Therapies to Complete Vestibulectomy in Select Patients with Neuroproliferative Vestibulodynia

ABSTRACT Introduction Complete vestibulectomy with vaginal advancement flap (CVVAF) for the treatment of neuroproliferative vestibulodynia (NPV) involves excision of the 1:00 to 11:00 region surrounding the urethral meatus and introitus, allowing the vagina and urethral meatus to be anastomosed to the vulva. The vestibule, however, extends above the urethral meatus and below the clitoris (12:00 region). In NPV patients, the entire vestibule including the 12:00 region contains excess mast cells/nerves, however the 12:00 region is not usually addressed during CVVAF surgery. While CVVAF surgery is associated with an approximately 80% success rate, we have observed some patients with significant pain at the 12:00 region pre-operatively who continue to have persistent entrance dyspareunia post-operatively. Objective We report on novel medical/surgical adjunctive strategies for NPV patients with pre-operative 12:00 pain implemented to reduce post-operative pain: using perineural 5% dextrose injection treatments pre-operatively; and performing a limited central core excision of the 12:00 vestibule during CVVAF. Perineural 5% dextrose injections have been shown to reduce neuropathic pain, in part by blocking the transient receptor potential vanilloid - TRPV-1 receptor. Methods In patients scheduled for CVVAF to treat suspected NPV, we performed preoperative vulvoscopy and baseline cotton-tip swab testing at the 12:00 region. In those with significant pain/tenderness at 12:00 (&amp;gt; 4/10 pain), we offered pre-operative perineural 5% dextrose treatments for the three days prior to CVVAF. Each day, cotton-tip swab testing of the 12:00 region was repeated prior to application of local anesthesia with 20% benzocaine, 8% lidocaine, 6% tetracaine. After anesthesia was established, betadine was applied to the region. Insulin syringes (31-gauge needle, 5/16”, 1 ml) filled with 5% dextrose were administered at six locations (total 6 ml) circling the 12:00 region, and compression applied for three minutes. The day after the final treatment, the patient underwent CVVAF including central core excision of the 12:00 region. All vestibular specimens were sent for immunohistochemical staining. Results 14 women, mean age 29 ± 9 years, had 12:00 pain &amp;gt; 4/10 on cotton swab testing at baseline, and confirmed immunohistochemical findings of excess mast cells/nerves consistent with NPV in all specimens. Baseline cotton-tip swab testing mean pain score prior to treatment was 7.3/10 (range 5-10/10) involving the entire 12:00 region. After three perineural 5% dextrose injection treatments, the cotton-tip swab testing mean pain score was reduced to 2.8/10 (range 0-5/10), focused on the central core region of the 12:00 vestibule. Side effects of perineural 5% dextrose injection were limited to mild bruising at injection sites in all patients. The central core excised specimens included the 12:00 minor vestibular gland ostia, and was oval-shaped, on average 2 mm thick, 6 mm wide and 7 mm long. Interrupted vertical sutures of 3-0 vicryl allowed for a horizontal closure of the defect. In patients who returned for in-person post-operative vulvoscopy at 6 months, the post-op cotton-tip swab testing mean pain score was 2.3/10 (range 0-4/10). Conclusions While more research is needed, preliminary results with these adjunctive therapies in selective NPV patients are encouraging. Disclosure No

Comparative antimicrobial efficacy of oregano oil, chlorhexidine, and sodium hypochlorite against Enterococcus faecalis: An in vitro study

Objective: The purpose of this study was to evaluate the comparative antibacterial efficacy of 0.2% oregano oil, 2% chlorhexidine (CHX), and 3% sodium hypochlorite (NaOCl) in disinfection of dentin tubules contaminated with Enterococcus faecalis.Materials and Method: One hundred and twenty human extracted anterior teeth were infected with E. faecalis for 21 days. They were assigned into three groups (n = 40) – Group 1: 3% NaOCl, Group 2: 2% CHX, and Group 3: 0.2% oregano oil. Disinfection protocol was followed using 31-gauge side-vented needle. After chemomechanical preparation, the apical 5 mm of the roots was removed frozen in liquid nitrogen and pulverized to expose E. faecalis in dentinal tubules. The number of colony-forming units of E. faecalis per mg dentin was determined. The data were analyzed statistically.Results: Zone of inhibition of oregano oil was found to be 15 mm, and the values were significant in Group III (P < 0.05) as compared to the other groups assessed.Conclusion: Within the study's limitation, 0.2% oregano oil showed better disinfection property against E. faecalis among tested irrigants. Therefore, it can be used as an effective alternative root canal irrigant.

Chitosan-Polycaprolactone Core-Shell Microparticles for Sustained Delivery of Bevacizumab.

The current therapy for treating neovascular age-related macular degeneration requires monthly intravitreal injection of angiogenesis inhibitors such as bevacizumab or ranibizumab via a 31-gauge needle to inhibit choroidal neovascularization. However, repeated intravitreal injections are associated with poor patient compliance and potential side effects. Microparticle-based injectable devices have shown great promise to address this issue by sustained delivery of protein therapeutics, but critical barriers remain, including limited loading capacity and steady long-term release without compromising the anti-angiogenic activity of drugs. Addressing these challenges, we developed a unique method for synthesizing biodegradable polymer-based core-shell microparticles with sizes around 10 μm, high physical integrity, and uniform size. Subsequent electrostatic and physical interactions to control protein diffusion were designed for the core-shell microparticles to effectively increase the capacity of drug loading to 25%, reduce burst release by almost 30%, and extend the period of drug release from 3 to 6 months. Remarkably, the microparticles enabled a longer-term drug administration and maintained high drug potency up to 6 months in vitro, representing significant advancement compared to conventional microparticle-based delivery platforms or currently commercialized devices. Additionally, the microparticles presented minimal toxicity to human retinal cells in vitro with over 90% cell viability, and they also exhibited good injection feasibility through 31-gauge needles in an ex vivo porcine eye model. These results warrant further studies to evaluate the clinical potential for treating posterior ophthalmic diseases as well as other conditions or injuries requiring long-term local drug administration.

A Study to Examine the Effect of Needle Gauge on Pain Perception in Patients Receiving Treatment With Botulinum Toxin in 2 Different Anatomical Areas

Botulinum toxin injection for treatment of rhytids is the commonest cosmetic intervention undertaken worldwide. It requires re-treatment at 3-month intervals for the effect to remain. Consequently, patient comfort is paramount in order for the procedure to remain acceptable. Intuitively, patients expect that smaller needles will be less painful, and this study examines the pain caused by needles of 2 gauges (31 and 32) when administering botulinum toxin in 2 anatomical areas. Patients were randomized into having the left or right side of their face treated with either a 31- or 32-gauge needle during botulinum toxin administration. Participants were asked to determine whether the left- or right-side treatment was most painful. The study was repeated in the glabellar and paraorbital regions. A total of 103 participants entered the study; 98 had the glabellar region treated and 76 the crow’s feet, and 72 patients had both regions treated. For the glabellar region, the smaller 32-gauge needle was significantly more painful than the larger 31-gauge needle ( P &lt; .01). There was no difference in patient’s pain perception between gauges of needle when treating the crow’s feet area ( P = .9). The 31-gauge needles produce significantly less pain than smaller 32-gauge needles when treating the glabellar region with botulinum toxin, but not in the periorbital region. We propose that this is due to differences in fascial adherence between the 2 areas. Consequently, we would recommend administering botulinum toxin with a 31-gauge needle in all areas.

Injectable gelatin hydroxyphenyl propionic acid hydrogel protects human retinal progenitor cells (hRPCs) from shear stress applied during small-bore needle injection

Many progenitor and stem cell-based therapies in pre-clinical development and in clinical trial have failed to achieve desired outcomes, in part, due to: low cell viability; dispersion of cells from the injection site; and/or failure of the cells to differentiate and engraft into host tissue. These problems may be exacerbated by the elevated shear stress applied to the cells as they pass through a small-bore needle. Our supposition is that these issues can be mitigated by replacing the phosphate buffered saline (PBS), which is likely employed as the cell carrier, with an injectable gelatin-based hydrogel incorporating an appropriate regulatory molecule (human epidermal growth factor). The first objectives of the study were to evaluate in vitro: the effects of injection through a 31-gauge needle on viability, proliferation, and phenotypic expression of human retinal progenitor cells (hRPCs), when employing PBS as the carrier and compare it to a gelatin-based gel as a carrier. The second objective of the work, conducted in vivo, in a rat model, was to: determine the degree of engraftment of injected cells; and evaluate markers of an immune response to the xenogeneic cells.Hydroxyphenyl propionic acid was conjugated to gelatin (Gtn-HPA) to enable in situ, enzyme-mediated covalent cross-linking, with independent control over the gelation time and degree of cross-linking. After 1 and 6 culture days, hRPC exposed to shear stress showed 50% or more reduction in viability of cells in PBS compared to cells in medium and in gel. Shear stress decreased proliferation and increased apoptosis in the PBS group by 50% or more, while cells in the gel group were protected from shear-induced apoptosis and their proliferation remained 2-fold higher than the PBS group. Also, of note was the preservation of or increase in stemness markers in the gel with hEGF group compared to cells in PBS and the gel alone, with or without shear stress. In vivo studies, performed 3 days after subretinal injection into non-immunosuppressed rats revealed: a) a greater number of cells at the injection site in the gel group, with signs of engraftment of cells to the retina; and b) a significantly lower immune response in the gel group, compared to cells injected in PBS.This work demonstrates that the shear stress experienced by hRPCs in PBS as a result of injection through a small-bore needle adversely affects cell viability, proliferation, apoptosis, phenotype, in vivo retention of cells at the injection site, migration, engraftment and immune reaction. These findings suggest the use of a biomaterial hydrogel as a replacement for PBS for retinal cell therapy.

Needle Gauge Influences Pain Perception During Intrapulpal Anaesthesia - A Randomized Clinical Trial.

Objective:The purpose of this randomized trial was to assess the pain perception during intrapulpal anesthesia (IP) using thinner gauge needles and syringes with or without topical anaesthesia as an adjunct.Methods:One hundred patients, on whom the inferior alveolar nerve block and intraligamentary injections failed, were recruited for the trial. Block randomization was performed and the patients were allocated into 4 groups based on the needle gauge and topical application of anaesthesia prior to IP injection. In two groups (27GN, 31GN) the patients received IP injection with 27 gauge or 31 gauge needles. The patients of other two groups received topical lignocaine-prilocaine mixture prior to the IP injection with 27 or 31 gauge needles, respectively (27GT, 31GT). The visual analogue scale (VAS) was used to assess the pain immediately after IP injection and after cleaning and shaping by a blinded outcome assessor. The Kruskal-Wallis test for overall comparisons followed by the post-hoc analysis using the Conover’s test (P<0.05) was done. Chi-square and Fischer exact test was used to assess the proportion of patients who were comfortable during IP anaesthesia.Results:The intensity of pain during IP administration with 31GN and 31GT (3.7 and 2.3 respectively) was significantly less in comparison to 27GN and 27GT (5.6 and 5.7 respectively). The proportion of patients who were significantly comfortable with IP injections in the groups 31GN and 31GT (52% and 80% respectively) were more (VAS<4) when compared to 27GN and 27GT (12% and 8% respectively). Topical application of lignocaine-prilocaine reduced the pain on IP injection significantly when used as an adjunct with 31 gauge needles. The anaesthetic success of IP anaesthesia was comparable and 100% (VAS scoring <4) in all the groups.Conclusion:Thinner gauge needles (31 gauge) significantly reduce pain perceived during IP anaesthesia. Topical anaesthesia with lignocaine-prilocaine acts as an effective adjunct only with 31gauge needle.

The Preventive Effect of Oxytocin on Retinopathy in Streptozotocin-Induced Diabetic Rats

Objectives:The aim of this study was to investigate the impact of intravitreal and intraperitoneal use of oxytocin (OT) on retinopathy in streptozotocin-induced diabetic rats.Materials and Methods:Twenty-four 6-8-week-old adult male and female Sprague Dawley rats were used in the study. Diabetes was induced in the rats with a single injection of intraperitoneal streptozotocin. Diabetes was verified after 48 hours by measuring blood glucose levels of 260 mg/dl (14.4 mmol/L) or higher in diabetic rats. The rats were divided into 4 groups and treated as follows: intravitreal physiological saline group (0.01 mL saline weekly), intravitreal OT group (10 μU/μL OT weekly), intraperitoneal physiological saline group (1 mL daily), and intraperitoneal OT group (100 IU/kg OT daily). Hamilton syringes fitted with 27-gauge needles were used for intraperitoneal injections while 31-gauge needles were used for intravitreal injection. After 4 weeks of treatment the rats were euthanized to evaluate outer nuclear layer (ONL) thickness, vascular endothelial growth factor (VEGF) immunoexpression, and plasma VEGF levels from blood samples obtained by cardiac puncture.Results:Morphometric analysis of retinal cross-sections showed that intravitreal and intraperitoneal OT significantly increased ONL thickness compared to physiological saline-treated groups. Also, OT treatment significantly decreased VEGF protein expression compared with the physiological saline groups. Plasma VEGF level was significantly higher in the physiological saline treatment group compared to the OT treatment group.Conclusion:OT reduces diabetic retinopathy progression, particularly when administered intravitreally. To our knowledge, this is the first attempt to investigate the impact of OT on diabetic retinopathy and may provide a new area for further research.

Botulinum Toxin Therapy

Clostridium botulinum toxin is effective through cleaving presynaptic proteins at the neuromuscular junction, which prevents the release of acetylcholine and inhibits muscle contraction. Several serotypes of botulinum toxin (BT) exist; however, only 2 types have been approved by the US Food and Drug Administration for commercial and medical use, A and B. Both types of BT must be administered intramuscularly with a syringe, but the type of syringe is the injector's preference. Which syringe type is most efficient in minimizing product waste and most cost-effective for the patient and provider? We performed a single-center, open-label, analytical study using BT therapy and 2 types of syringes for analytics of cost-effectiveness. OnabotulinumtoxinA was the neuromodulator used in this report. Vials (100 U) of BT A were each reconstituted with 2.5 mL of 0.9% sodium chloride, for a final concentration of 4 U/0.1 mL. High-dead-space syringes are compared with low-dead-space syringes: 1-mL tuberculin (TB) luer slip syringe with detachable 25-gauge needle and 1-mL ultrafine insulin syringe with an attached 31-gauge needle, respectively. After each syringe was evacuated, the TB syringe was noted to contain 0.05 mL of the remaining product in the hub. Providers are discarding approximately 2 U of BT per TB syringe product injection. If the physician uses 30 syringes per day, 3 days a week, for 1 year, it equals to a lost revenue of approximately $155,500 per year. To individualize the cost-effective analysis, average quantity of syringes used per patient and overall patient volume must be considered, with corresponding adjustment of cost and units discarded. The American Society of Plastic Surgeons reported that the use of neuromodulators has increased by approximately 797% from 2000 to 2016. During that period, the price of neuromodulators has also increased by approximately 85%. Considering these statistics, the type of syringe used for BT neuromodular injection is a thought-provoking concept but surrounded by a paucity of data. Overall, our data suggest that the use of ultrafine insulin syringes for injection of BT reduces product waste and is cost-effective for the patient and the provider.

Biocompatible Reverse Thermal Gel Sustains the Release of Intravitreal Bevacizumab In Vivo

We assessed the in vivo release profile of bevacizumab from and biocompatibility of poly(ethylene glycol)-poly-(serinol hexamethylene urethane), or ESHU, a thermoresponsive hydrogel administered intravitreally for drug delivery. The technical feasibility of injection was assessed quantitatively via mechanical testing. For in vivo studies, New Zealand White rabbit eyes were injected intravitreally with 0.05 mL of either: ESHU dissolved in 25 mg/mL bevacizumab, ESHU dissolved in PBS, or 25 mg/mL bevacizumab. Clinical examination included IOP measurements and examination with indirect ophthalmoscopy for signs of inflammation. Additionally, eyes were examined histologically following euthanasia. To quantify bevacizumab release, aqueous humor samples were obtained via anterior chamber paracentesis and ELISA was used to determine the concentration of drug weekly. In vitro cytotoxicity testing also was performed using bovine corneal endothelial cells. The ESHU was injected easily through a 31-gauge needle, was well tolerated in vivo, and caused minimal cell death in vitro when compared to other common materials, such as silicone oil. The long-term presence of the gel did not affect IOP, and there was no evidence of inflammation histologically or through indirect observation. The ESHU sustained the release of bevacizumab for over 9 weeks and maintained a drug concentration that averaged 4.7 times higher than eyes receiving bolus bevacizumab injections. To our knowledge, this is the first report demonstrating sustained bevacizumab release in vivo from an intravitreally injected hydrogel formulation, suggesting that this delivery system may be a promising candidate for ocular drug delivery.

A micro-advancer device for vitreal injection and retinal recording and stimulation

A micro-advancer device that positions a narrow-gauge needle within the vitreous humor of the rat eye is described. The device is compact, simple and inexpensive to manufacture. It consists of an outer guard needle and an inner injection needle that is advanced through the guard needle. With the rat held in a stereotaxic holder and the globe fixed to a stabilizing ring, the outer 25-gauge guard needle is advanced through the sclera using a standard micromanipulator. The inner 31-gauge injection needle is then advanced through the guard needle with a manually controlled leadscrew and carriage mechanism. The inner injection needle is attached to a Hamilton syringe and can be positioned to within microns of the retinal surface under visual observation through a microscope. The injection needle is fixed to the device by a quick-release clamp on the carriage and can be rapidly exchanged while the guard needle remains in place in the vitreous. This permits different solutions to be injected sequentially into the vitreous humor. Recording electrodes, stimulating electrodes, and optical fibers can also be advanced through the guard needle and positioned accurately near the retinal surface or within the retina.

&lt;b&gt;The study of migraine model rat with photophobia &lt;/b&gt;&lt;b&gt;in the upper cervical spinal cord &lt;/b&gt;

Background and purposes: Photophobia is characteristic and important sign of the migraine headache. Recently, we found that the response of dura-sensitive neuron to photic stimulation was enhanced after dura inflammation. Some previous papers also have reported that neurons located in the dorsal horn of the C2 spinal cord (C2 neurons) receive photic inputs suggesting that C2 neurons somehow involved in photophobia. However, how the C2 neurons are involved in photophobia associated with migraine is unknown. Therefore, the change in neuronal excitability of C2 nociceptive neurons was analyzed in rat model with dural inflammation. Methods: The Sprague-Dawley rats were anesthetized with pentobarbital sodium (50 mg/kg, i.p.) and the small hole was made in the frontal bone, and 10% mustard oil (MO) was applied to the dura surface around the transverse sinus (migraine rat). Photic stimulation was applied to the eye in migraine and vehicle-treated rats, and c-Fos like immunoreactive (LI) cells and pERK-immunoreactive (IR) cells in C2 were precisely analyzed. To identify trigeminal ganglion (TG) neurons innervating the retina, the fluorogold (FG) solution (4% in distilled water, 10 µl) was injected to the retina using a 31-gauge needle. Substance P (SP), calcitonin generelated peptide (CGRP), TRPV1 immunoreactivities were also detected in the ratina. Results: Following MO application to the dura, a large number of c-Fos-LI cells was expressed in the transition zone between subnuclei interpolaris and caudalis (Vi/Vc) zone bilaterally and was also in the ipsilateral C2. Photic stimulation to the eye in migraine rat caused an expression of pERK-IR cells in C2, and many of them also showed c-Fos immunoreactivity. FG-labeled trigeminal ganglion cells were observed in the first branch-innervated area of the TG following FG injection into the retina. Many SP, CGRP and TRPV1 immunoreactivities were detected in nerve fibers in the retina. The present findings suggested that C2 neurons are involved in photophobia associated with migraine, and also suggested that the unmyelinated trigeminal afferents innervating the retina might be one of the sources of photic information in photophobia.

Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

Atrial natriuretic peptide (ANP) is a hormone with diuretic, natriuretic, and vasodilatory properties. ANP blocks vascular endothelial growth factor (VEGF) production and signaling in vitro; however, its role in vascular leakage and angiogenesis is unknown. In vitro, retinal barrier permeability (transepithelial electrical resistance (TEER)) was measured in cultured retinal endothelial (HuREC) and retinal epithelial (ARPE-19) cells with VEGF (10 ng/ml), ANP (1 pM to 1 micromol/L), and/or isatin, an ANP receptor antagonist. In vivo, blood-retinal barrier (BRB) leakage was studied using the Evans Blue dye technique in rats treated with intravitreal injections of ANP, VEGF, or vehicle. Choroidal neovascularization was generated by laser injury, and 7 days later, lesion size and leakage was quantitated. ANP significantly reversed VEGF-induced BRB TEER reduction in both HuREC and ARPE-19 cells, modeling the inner and the outer BRB, respectively. Isatin, a specific ANP receptor antagonist, reversed ANP's effect. ANP reduced the response of ARPE-19 cells to VEGF apically but not basolaterally, suggesting polarized expression of the ANP receptors in these cells. ANP's TEER response was concentration but not time dependent. In vivo, ANP significantly reduced VEGF-induced BRB leakage and the size of laser-induced choroidal neovascularization lesions. In sum, ANP is an effective inhibitor of VEGF-induced vascular leakage and angiogenesis in vivo. These results may lead to new treatments for ocular diseases where VEGF plays a central role, such as age-related macular degeneration or diabetic retinopathy.

A Comparison of Injection Force and Dosage Scale Size Between NovoPen®3 and NovoPen®4

Easy-to-use insulin devices are an important tool in the treatment of diabetes. In this study, injection force requirements and dosage scale displays were evaluated for NovoPen 3 and NovoPen 4 (both from Novo Nordisk A/S, Copenhagen, Denmark). To simulate 5 years of expected lifetime usage, 5,475 injections were performed automatically. Before and after lifetime testing, the force required to expel 60 U of insulin from NovoPen 3 and NovoPen 4 with 30-gauge or 31-gauge needles was measured. To compare dosage scale displays, digital images of multiple settings were made, and the total inked areas of digits were converted to mm(2). At baseline, the mean +/- SD injection force of NovoPen 4 was 9.14 +/- 0.87 N and 16.55 +/- 1.17 N, which was significantly lower (P < 0.001) than for NovoPen 3, at 18.36 +/- 1.06 N and 29.81 +/- 1.26 N, with the 30-gauge and 31-gauge needle, respectively. After simulated lifetime testing, mean +/- SD injection force was 10.93 +/- 0.77 N and 17.77 +/- 1.14 N for NovoPen 4, which was significantly lower than the injection force of 18.54 +/- 0.94 N and 31.69 +/- 1.98 N for NovoPen 3 (P < 0.001). The mean dosage scale digit size was 1.63 mm(2) for NovoPen 3 and 7.82 mm(2) for NovoPen 4, with a mean difference of 6.19 mm(2). The display for NovoPen 4 was 4.74 times larger (P < 0.001). The mean injection force required to operate NovoPen 4 was reduced up to 50% compared with NovoPen 3 (P < 0.001), and the mean dosage display for NovoPen 4 was over four times larger than for NovoPen 3 (P < 0.001). Based on these findings, patients with diabetes who have manual or visual impairment should find it easier to dose insulin with NovoPen 4.

Comparison of Usability and Patient Preference for Insulin Pen Needles Produced with Different Production Techniques: “Thin-Wall” Needles Compared to “Regular-Wall” Needles: An Open-Label Study

People with diabetes mellitus on insulin therapy increasingly prefer insulin pens over syringes and vials. Different types of pen needles are available for insulin pens, e.g., "thin-wall" needles, which have the same outer diameter but a relatively lager inner diameter compared to needles produced with a "regular-wall." We conducted a multicenter open-label, single-arm study in patients (n = 97) with diabetes mellitus using insulin pens. The aim of our study was to evaluate pen user habits as well as to assess patient's appraisals and ratings considering two different types of 31-gauge pen-needles, so-called "thin-wall" needles or "regular-wall" needles." Patients twice underwent a 2-week intervention period, starting with a "regular-wall period" followed by a "thin-wall-period." After each period patients filled in questionnaires. In total, 97 diabetes patients (48% female; mean age, 56 years; range, 20-70 years) completed the study. Patients reported significantly less pain, less bleeding, less skin irritation, less injection strain, less residual insulin leakage from the needle tip after injection, and less needle occlusion when using "thin-wall needles" (P < 0.001). A higher proportion of patients expressed an overall preference for the "thin-wall" needles (78%) compared to the "regular-wall" needles (8%) (P < 0.001). Pen and pen needle handling, preparation, and execution of injections should be a part of repeated diabetes education and be re-evaluated on a regular basis. The "thin-wall" 31-gauge needle was found to be more user-friendly and consequently preferred by the patients. Additional larger-scale trials using blinded and randomized study designs are needed to validate these findings.

A blood sampling microsystem for pharmacokinetic applications: Design, fabrication, and initial results

This paper describes a microsystem for automated blood sampling from laboratory mice used in pharmacokinetic studies. Intended to be mounted as a "backpack" on a mouse, it uses a microneedle, reservoir, and an actuator to instantaneously prick the animal for a time-point sample, eliminating the need for a tethered catheter with large dead volume. The blood is collected by capillary effect through a 31-33 gauge microneedle (250-210 microm OD) into a approximately 1 microL micromachined steel reservoir. The voice coil actuator provides a peak force of approximately 300 mN, which amply exceeds the measured piercing force of mouse skin (i.e., 60-85 mN for a 31-gauge needle with 12 degrees bevel). The sampling system was tested in vitro using a mock vessel with adjustable pressure; the reservoir was filled in <0.15 s by a combination of the capillary effect and blood pressure. The system may also be used to sample interstitial fluid, but the absence of blood pressure makes it necessary to enhance the capillary effect of the needle. This is accomplished by either electropolishing the inner surface to make it more hydrophilic or using a polymer wire insert to increase the surface area. The steel surface of the reservoir is also coated with silicon oxynitride by plasma-enhanced chemical vapor deposition to improve its hydrophilicity. Blood from fresh bovine tissue was collected into the reservoir to simulate interstitial fluid sampling. In vivo tests on live, anesthetized mice resulted in successful collection of blood into the reservoir. The possible integration of the device in microanalytical systems and the device scalability for multisampling are discussed.

경락추적을 위한 피내 알시안 블루 주입방법

Objective In this article, we report on the intradermal Alcian blue staining method for tracing the meridians of acupuncture. Methods 1% Alcian blue solution was injected into acupoints by using a 0.5mL insulin syringe with a 31-gauge needle, then the skin was incised and was observed under a stereoscopic microscope. The specimens were examined by using immunohistochemical methods and were observed under a confocal laser scanning microscope. Results A threadlike structure, which was visualized with Alcian blue, existed in dermis layer and proceeded to hypodermis. In this structure, characteristic alignments of rod- shaped nuclei and sized DNA granules were observed. Furthermore, abundant blood capillary plexuses, peripheral nerve endings, and a corpuscle-like structure(about in diameter) were visualized in the skin tissues of acupoints. Conclusion It was concluded that the specific threadlike and corpuscle-like structures corresponded to superficial Bonghan duct and corpuscle, respectively.

A Randomized Study to Evaluate Injection Site Reactions using Three Different Enfuvirtide Delivery Mechanisms (the OPTIONS Study)

The antiretroviral enfuvirtide (ENF) is injected subcutaneously using a 27-gauge needle. Injection site reactions (ISRs) can affect long-term ENF tolerability. Alternative ENF delivery methods may ameliorate ISRs. We conducted a multicentre, open-label, randomized controlled trial in which patients receiving ENF were randomized to continue receiving ENF by a 27-gauge needle, a shorter 31-gauge needle or a gas-powered, needle-free injection device (NFID). The primary study endpoint was the proportion of participants with < grade 2 ISR induration at week 12. Sixty patients received treatment and were included in the intention-to-treat population. The cohort was predominantly male (95%) with a mean age of 49.1 (SD +/- 7.7) years who had injected ENF for a mean of 821 (SD +/- 561) days. Response rates for ISR induration at week 12 were 38%, 25% and 42% for the 27-gauge, 31-gauge and NFID groups, respectively (all pairwise treatment comparison P-values > 0.2). There was no significant between-group difference for any ISR endpoint, except for changes in the composite ISR score (that is, no ongoing pain of > grade 1 or ISR for ongoing pain > or = grade 1 with induration ISR < grade 3 and for nodules < grade 2), which favoured the 27-gauge needle and NFID groups over the 31-gauge group (P = 0.012 and 0.047, respectively). Plasma HIV RNA load was unaffected. There were seven adverse events related to the delivery system: five attributed to the NFID. At week 12, 85% of participants elected to use the NFID. Needle-free ENF injection offers a reasonable, reliable alternative to needle-based injecting in this population, at least in the short term.