Weak Kappa Research Articles

Functional, clinical, and radiological outcomes of split anterior tibial tendon transfers in patients with sequelae of congenital talipes equinovarus.

This retrospective analysis aimed to assess the effectiveness of Split Tibialis Anterior Tendon Transfer (Split TATT) in treating residual idiopathic congenital talipes equinovarus (CTEV) deformities. 15 patients (20 feet) with CTEV, with a mean age of 6.4 ± 3.2 years, initially treated with Ponseti casting, underwent Split TATT. Clinical and radiological evaluations, including Diméglio and Garceau scores, dorsiflexion, and X-ray measurements, were conducted preoperatively and post-operatively at a minimum 2-year follow-up. Significant improvements were observed in Diméglio and Garceau scores. Dorsiflexion increased by an average of 3°, and radiological analysis revealed nuanced changes. Despite a weak Kappa coefficient, positive trends in dorsiflexion and Garceau scores were noted. Preoperative Garceau scores did not reliably predict postoperative results. Split TATT demonstrates promising results in improving muscular balance and functional outcomes in CTEV. While radiological changes are subtle, positive trends in clinical scores indicate meaningful outcomes. IV Retrospective study.

From Seaweeds to Hydrogels: Recent Progress in Kappa-2 Carrageenans.

Hybrid carrageenans, also called kappa-2 (K2) or weak kappa, are a class of sulfated polysaccharides with thermo-reversible gelling properties in water and are extracted from a specific family of red seaweeds. K2 are known in the industry for their texturizing properties which are intermediate between those of kappa-carrageenans (K) and iota-carrageenans (I). As such, K2 are gaining industrial interest, as they can replace blends of K and I (K + I) in some niche applications. Over the last decade or so, some progress has been made in unravelling K2's chemical structure. The understanding of K2 gel's structure-rheological properties' relationships has also improved. Such recent progress is reported here, reviewing the literature on gelling K2 published since the last review on the topic. The focus is on the seaweeds used for extracting K2, their block copolymer chemical structures, and how these impact on the gel's formation and rheological properties. The outcome of this review is that additional rheological and structural studies of K2 hydrogels are needed, in particular to understand their viscoelastic behavior under large deformation and to unravel the differences between the texturizing properties of K2 and K + I.

Remote Digital Preoperative Assessments for Cleft Lip and Palate May Improve Clinical and Economic Impact in Global Plastic Surgery.

Reconstructive surgical care can play a vital role in the resource-poor settings of low- and middle-income countries. Telemedicine platforms can improve the efficiency and effectiveness of surgical care. The purpose of this study is to determine whether remote digital video evaluations are reliable in the context of a short-term plastic surgical intervention. The setting for this study was a district hospital located in Latacunga, Ecuador. Participants were 27 consecutive patients who presented for operative repair of cleft lip and palate. We calculated kappa coefficients for reliability between in-person and remote digital video assessments for the classification of cleft lip and palate between two separate craniofacial surgeons. We hypothesized that the technology would be a reliable method of preoperative assessment for cleft disease. Of the 27 (81.4%) participants, 22 received operative treatment for their cleft disorder. Mean age was 11.1 ± 8.3 years. Patients presented with a spectrum of disorders, including cleft lip (24 of 27, 88.9%), cleft palate (19 of 27, 70.4%), and alveolar cleft (19 of 27, 70.4%). We found a 95.7% agreement between observers for cleft lip with substantial reliability (κ = .78, P < .01). There was an 82.6% agreement between observers for cleft palate, with a moderate interrater reliability (κ = .55, P = .01). We found only a 47.8% agreement between observers for alveolar cleft with a nonsignificant, weak kappa agreement (κ = .06, P = .74). Remote digital assessments are a reliable way to preoperatively diagnose cleft lip and palate in the context of short-term plastic surgical interventions in low- and middle-income countries. Future work will evaluate the potential for real-time, telemedicine assessments to reduce cost and improve clinical effectiveness in global plastic surgery.

Chapter Two - Hybrid Carrageenans: Isolation, Chemical Structure, and Gel Properties

Hybrid carrageenan is a special class of carrageenan with niche application in food industry. This polysaccharide is extracted from specific species of seaweeds belonging to the Gigartinales order. This chapter focuses on hybrid carrageenan showing the ability to form gels in water, which is known in the food industry as weak kappa or kappa-2 carrageenan. After introducing the general chemical structure defining hybrid carrageenan, the isolation of the polysaccharide will be discussed focusing on the interplay between seaweed species, extraction parameters, and the hybrid carrageenan chemistry. Then, the rheological experiments used to determine the small and large deformation behavior of gels will be detailed before reviewing the relationships between gel properties and hybrid carrageenan chemistry.

The structure of κ/ι-hybrid carrageenans II. Coil–helix transition as a function of chain composition

This paper describes the effect of the κ/ι-ratio on the physical properties of κ/ι-hybrid carrageenans (synonyms: kappa-2, κ-2, weak kappa, weak gelling kappa). To this end, a series of κ/ι-hybrid carrageenans ranging from almost homopolymeric κ-carrageenan (98 mol-% κ-units) to almost homopolymeric-carrageenan (99 mol-% ι-units) have been extracted from selected species of marine red algae (Rhodophyta). The κ/ι-ratio of these κ/ι-hybrids was determined by NMR spectroscopy. Their rheological properties were determined by small deformation oscillatory rheology. The gel strength (storage modulus, G′) of the κ/ι-hybrids decreases with decreasing κ-content. On the other hand, the gelation temperature of the κ-rich κ/ι-hybrids is independent of their composition. This allows one to control the gel strength independent of the gelation or melting temperature. The conformational order–disorder transition of the κ/ι-hybrids was studied using optical rotation and high-sensitivity differential scanning calorimetry. High-sensitivity DSC showed that the total transition enthalpy of the κ/ι-hybrids goes through a minimum at 60 mol-% κ-units, whereas for the mixture of κ- and ι-carrageenan, the total transition enthalpy is a linear function of the composition. With respect to the ordering capability, the κ/ι-hybrid carrageenans seem to behave as random block copolymers with length sequence distributions truncated from the side of the small lengths. Intrinsic thermodynamic properties (e.g., transition temperature and enthalpy) of κ- and ι-sequences in these copolymers are close to those of their parent homopolymers. The critical sequence length for κ-sequences is 2-fold of that for ι-sequences.

Buprenorphine: a primer for emergency physicians.

The recent approval of office-based treatment for opioid addiction and US Food and Drug Administration approval of buprenorphine will expand treatment options for opioid addiction. Buprenorphine is classified as a partial micro opioid agonist and a weak kappa antagonist. It has a high affinity for the micro receptor, with slow dissociation resulting in a long duration of action and an analgesic potency 25 to 40 times more potent than morphine. At higher doses, its agonist effects plateau and it begins to behave more like an antagonist, limiting the maximal analgesic effect and respiratory depression. This "ceiling effect" confers a high safety profile clinically, a low level of physical dependence, and only mild withdrawal symptoms on cessation after prolonged administration. Suboxone contains a mixture of buprenorphine and naloxone. The naloxone is poorly absorbed sublingually and is designed to discourage intravenous use. Subutex, buprenorphine only, will also be available primarily as an initial test dose. Clinicians will be using this drug for detoxification or for maintenance of opioid addiction. Patients with recent illicit opioid use may develop a mild precipitated withdrawal syndrome with the induction of buprenorphine. Acute buprenorphine intoxication may present with some diffuse mild mental status changes, mild to minimal respiratory depression, small but not pinpoint pupils, and relatively normal vital signs. Naloxone may improve respiratory depression but will have limited effect on other symptoms. Patients with significant symptoms related to buprenorphine should be admitted to the hospital for observation because symptoms will persist for 12 to 24 hours.

Structure-activity relationships of dynorphin analogs substituted in positions 2 and 3.

Following up on the observation that the dynorphin analog [Pro(3)]Dyn A(1-11)-NH(2) 2 possesses high affinity and selectivity for the kappa opioid receptor, a number of related peptides were prepared and characterized by radioligand binding and [(35)S]GTPgammaS assays. While incorporation of 2-azetidine carboxylic acid in position 3 led to the equally potent analog 3, the corresponding analog containing piperidine-2-carboxylic acid showed a nearly 90-fold reduction in kappa affinity. Differential preferred bond angles phi in the three building blocks might account for these observations. Compounds 2 and 3 were kappa antagonists with IC(50) values of 380 and 350 nM, respectively. The Sar(3) analog 7 and the Sar(2) analog 8 were kappa agonists, with greater selectivity than Dyn A(1-11)-NH(2) 1. In view of their high kappa affinities (8: K(i) = 1.5 nM; 2: K(i) = 2.4 nM), the new analogs were surprisingly weak kappa agonists or antagonists, e.g., the EC(50) value for the agonist 8 was 280 nM. Different kappa receptor subtypes in binding vs functional assays can not account for these results, since both assays were performed using the same membrane preparation.

Methylated analogues of methyl (R)-4-(3,4-dichlorophenylacetyl)- 3-(pyrrolidin-1-ylmethyl)piperazine-1-carboxylate (GR-89,696) as highly potent kappa-receptor agonists: stereoselective synthesis, opioid-receptor affinity, receptor selectivity, and functional studies.

Analogues of the kappa-receptor agonist methyl (R)-4-(3,4-dichlorophenylacetyl)-3-(pyrrolidin-1-ylmethyl)piperazine-1-carboxylate (GR-89,696, 6) bearing an additional methyl substituent in the side chain are synthesized and evaluated for their kappa-receptor affinity and selectivity. A key step in the synthesis is the stereoselective reductive amination of the ketones 9, 18, and 19 with pyrrolidine and NaBH(3)CN, which succeeds only in the presence of the Lewis acid Ti(OiPr)(4). Whereas the BOC-substituted ketone 9 affords the unlike and like diastereomers of 10 in a ratio of 70:30, the diastereoselectivity during the reductive amination of the butyl and phenyl substituted ketones 18 and 19 is enhanced to 85:15 (butyl derivative) and >95:<5 (phenyl derivative) in favor of the unlike diastereomers. In receptor binding studies using the radioligand [(3)H]U-69,593 the (S,S)-configured methyl carbamate (S,S)-14 reveals the highest kappa-receptor affinity (K(i) = 0.31 nM) within this series, even exceeding the lead kappa-agonist 6 (GR-89,696). A slightly reduced kappa-receptor affinity is observed with the propionamide (S,S)-13 (K(i) = 0.67 nM). The kappa-receptor affinity of piperazines with acyl or alkoxycarbonyl residues at both nitrogen atoms (11, 13, 14) decreases in the order (S,S) > (R,R) > (S,R) > (R,S). The methyl carbamate (S,S)-14 discloses a unique activity profile also binding at mu-receptors in the subnanomolar range (K(i) = 0.36 nM). In a functional assay, i.e., by measuring acetylcholine release in rabbit hippocampus slices, the agonistic effects of the methyl carbamate (S,S)-14 and the propionamide (S,S)-13 are demonstrated. Only weak kappa- and mu-receptor affinities are found with the butyl- and phenyl-substituted piperazines 22 and 23. However, considerable sigma(1)-receptor affinity is determined for the enantiomeric, unlike-configured butyl derivatives (R,S)-22 and (S,R)-22 with K(i)-values of 40.2 nM and 81.0 nM, respectively.

Morphine antagonizes U50,488's effects in a squirrel monkey shock titration procedure.

To determine whether a mu opioid agonist modulates the effects of a kappa opioid agonist in squirrel monkeys responding under a shock titration procedure, morphine was administered in combination with an ED75 dose of U50,488. Morphine (0.03-0.3 mg/kg) did not alter U50,488's early peak effects (15-25 min post-injection), but dose dependently antagonized U50,488's later effects (40-100 min post-injection); these doses of morphine shifted the U50,488 dose-effect curve < 1/4 log unit to the right. After 6-8 weeks of daily morphine administration, higher doses of morphine (0.3-3.0 mg/kg) shifted the U50,488 dose-effect curve > 1/2 log unit to the right. Morphine still did not antagonize early peak effects of the ED75 dose of U50,488, but antagonized early and late effects of a lower dose. Thus, morphine is a weak kappa antagonist in the shock titration procedure. In addition to its low affinity for kappa receptors, morphine's kappa antagonist activity is limited by its mu agonist effects, particularly in the non-morphine-tolerant monkey.